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  • 97
    Sino Biological ago2
    Schematic model showing the essential role of <t>AGO2</t> in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.
    Ago2, supplied by Sino Biological, used in various techniques. Bioz Stars score: 97/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/ago2/product/Sino Biological
    Average 97 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    ago2 - by Bioz Stars, 2021-04
    97/100 stars
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    97
    Thermo Fisher lipofectamine
    Schematic model showing the essential role of <t>AGO2</t> in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.
    Lipofectamine, supplied by Thermo Fisher, used in various techniques. Bioz Stars score: 97/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/lipofectamine/product/Thermo Fisher
    Average 97 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    lipofectamine - by Bioz Stars, 2021-04
    97/100 stars
      Buy from Supplier

    86
    Sino Biological negr1
    Schematic model showing the essential role of <t>AGO2</t> in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.
    Negr1, supplied by Sino Biological, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/negr1/product/Sino Biological
    Average 86 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    negr1 - by Bioz Stars, 2021-04
    86/100 stars
      Buy from Supplier

    99
    Promega viafect transfection reagent
    Schematic model showing the essential role of <t>AGO2</t> in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.
    Viafect Transfection Reagent, supplied by Promega, used in various techniques. Bioz Stars score: 99/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/viafect transfection reagent/product/Promega
    Average 99 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    viafect transfection reagent - by Bioz Stars, 2021-04
    99/100 stars
      Buy from Supplier

    Image Search Results


    Schematic model showing the essential role of AGO2 in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: Schematic model showing the essential role of AGO2 in PDAC progression. Expression of KRAS G12D in normal pancreatic cells initiates low grade PanINs which progress to higher grade PanINs, PDAC, and metastases. PanIN formation requires EGFR that can phosphorylate AGO2 to disrupt the KRAS-AGO2 interaction and is, therefore, AGO2-independent. PDAC progression is associated with increased expression of KRAS and AGO2 at the membrane. AGO2 ablation results in increased expression of microRNAs that regulate cell proliferation and senescence and also activates KRAS to promote oncogene-induced senescence. OIS due to AGO2 loss prevents progression of low grade PanINs to PDAC and leads to infiltration by natural killer (NK) cells.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Expressing

    Increased membrane co-localization of RAS and AGO2 during PDAC progression. a RAS10 (panRAS) antibody specificity for IHC and IF analyses was determined by staining RASless MEFs rescued by either oncogenic KRAS or BRAF V600E . Scale bar, 100 µm. b Membranous RAS staining in 10-week-old PanINs of mouse tissues expressing oncogenic KRAS using either IHC (left) or IF (right). Scale bars, 50 µm. c Peptide competition assay to demonstrate specificity of the RAS10 antibody in mouse tissues expressing oncogenic KRAS . Representative IF images using the RAS10 antibody pre-incubated with RAS peptide spanning the antibody epitope 30-39aa and control overlapping RAS peptide spanning 34-43aa. Scale bar, 50 µm. d Representative images of AGO2 IF analysis in pancreatic tissues from AGO2 +/+ ; KRAS G12D ; p48Cre and AGO2 fl/fl ;KRAS G12D ; p48Cre mice. Scale bar, 50 µm. e Representative images of IF analysis for RAS and AGO2 through PDAC progression in the AGO2 +/+ ; KRAS G12D ; p48Cre mice. Scale bar, 50 µm. f Representative images of IF analysis of human pancreatic tissue on a TMA showing co-localization of AGO2 and RAS in PanIN and PDAC cells. For ( e ) and ( f ), numbers adjacent to merged images indicate the Pearson’s coefficient of co-localization (PCC) of RAS-AGO2 signals at the membranous regions (where 0 is no overlap and 1 is complete overlap). PCC was determined using co-localization signals of at least 50 cells in three distinct areas representative of normal acinar, PanIN, PDAC, or metastases. Scale bar, 50 µm. g Representative images of Proximity Ligation Assay (PLA), performed to detect either RAS (RAS PLA) or AGO2 (AGO2 PLA) expression and the RAS-AGO2 interaction (RAS-AGO2 PLA) within PanIN lesions of AGO2 +/+ ; KRAS G12D ; p48Cre (upper panel) and AGO2 fl/fl ;KRAS G12D ; p48Cre (lower panel) mice. PLA signals appear as red dots around DAPI stained nuclei in blue. Scale bar, 50 µm.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: Increased membrane co-localization of RAS and AGO2 during PDAC progression. a RAS10 (panRAS) antibody specificity for IHC and IF analyses was determined by staining RASless MEFs rescued by either oncogenic KRAS or BRAF V600E . Scale bar, 100 µm. b Membranous RAS staining in 10-week-old PanINs of mouse tissues expressing oncogenic KRAS using either IHC (left) or IF (right). Scale bars, 50 µm. c Peptide competition assay to demonstrate specificity of the RAS10 antibody in mouse tissues expressing oncogenic KRAS . Representative IF images using the RAS10 antibody pre-incubated with RAS peptide spanning the antibody epitope 30-39aa and control overlapping RAS peptide spanning 34-43aa. Scale bar, 50 µm. d Representative images of AGO2 IF analysis in pancreatic tissues from AGO2 +/+ ; KRAS G12D ; p48Cre and AGO2 fl/fl ;KRAS G12D ; p48Cre mice. Scale bar, 50 µm. e Representative images of IF analysis for RAS and AGO2 through PDAC progression in the AGO2 +/+ ; KRAS G12D ; p48Cre mice. Scale bar, 50 µm. f Representative images of IF analysis of human pancreatic tissue on a TMA showing co-localization of AGO2 and RAS in PanIN and PDAC cells. For ( e ) and ( f ), numbers adjacent to merged images indicate the Pearson’s coefficient of co-localization (PCC) of RAS-AGO2 signals at the membranous regions (where 0 is no overlap and 1 is complete overlap). PCC was determined using co-localization signals of at least 50 cells in three distinct areas representative of normal acinar, PanIN, PDAC, or metastases. Scale bar, 50 µm. g Representative images of Proximity Ligation Assay (PLA), performed to detect either RAS (RAS PLA) or AGO2 (AGO2 PLA) expression and the RAS-AGO2 interaction (RAS-AGO2 PLA) within PanIN lesions of AGO2 +/+ ; KRAS G12D ; p48Cre (upper panel) and AGO2 fl/fl ;KRAS G12D ; p48Cre (lower panel) mice. PLA signals appear as red dots around DAPI stained nuclei in blue. Scale bar, 50 µm.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Immunohistochemistry, Staining, Expressing, Competitive Binding Assay, Incubation, Mouse Assay, Periodic Counter-current Chromatography, Proximity Ligation Assay

    ARS-1620, a G12C-specific inhibitor, disrupts the KRAS G12C -AGO2 interaction. IP of endogenous AGO2 followed by immunoblot to detect KRAS in KRAS G12C harboring ( a ) H358 and ( b ) MIA PaCa-2 cells treated with varying concentrations of ARS-1620 for three and nine hours, respectively. KRAS G12D harboring ( c ) Panc 05.04 and ( d ) Panc 10.05 cells, respectively, treated with ARS-1620 for 24 h followed by AGO2 IP and immunoblot analysis of KRAS G12D . For each cell line, input blots for AGO2 and RAS are shown.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: ARS-1620, a G12C-specific inhibitor, disrupts the KRAS G12C -AGO2 interaction. IP of endogenous AGO2 followed by immunoblot to detect KRAS in KRAS G12C harboring ( a ) H358 and ( b ) MIA PaCa-2 cells treated with varying concentrations of ARS-1620 for three and nine hours, respectively. KRAS G12D harboring ( c ) Panc 05.04 and ( d ) Panc 10.05 cells, respectively, treated with ARS-1620 for 24 h followed by AGO2 IP and immunoblot analysis of KRAS G12D . For each cell line, input blots for AGO2 and RAS are shown.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques:

    AGO2 modulates microRNAs and limits RAS activation to control OIS. a Plot showing relative expression of microRNAs from pancreata obtained from three mice from each of the indicated genotypes at the 500-day time point. Log fold change values were generated relative to microRNA expression in three p48Cre mice (used as reference). Two sided t -tests were performed to determine the P value and error bars are mean values +/− SEM. b GSEA (Gene Set Enrichment Analysis) of transcriptional changes significantly enriched (FDR value

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: AGO2 modulates microRNAs and limits RAS activation to control OIS. a Plot showing relative expression of microRNAs from pancreata obtained from three mice from each of the indicated genotypes at the 500-day time point. Log fold change values were generated relative to microRNA expression in three p48Cre mice (used as reference). Two sided t -tests were performed to determine the P value and error bars are mean values +/− SEM. b GSEA (Gene Set Enrichment Analysis) of transcriptional changes significantly enriched (FDR value

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Activation Assay, Expressing, Mouse Assay, Generated

    Phosphorylation of AGO2 Y393 disrupts its interaction with KRAS. a Immunoprecipitation (IP) of endogenous AGO2 upon EGF stimulation (5′) in the indicated cancer cells expressing wild-type RAS followed by immunoblot analysis of KRAS. For MCF7 cells, endogenous co-IP analysis was performed using both AGO2 and KRAS-specific antibodies. For each cell line and panel in this figure, MAPK activation and levels of various proteins are shown as input blots. b IP of endogenous AGO2 upon EGF stimulation (5′), in the indicated cancer cells harboring different KRAS mutations, followed by immunoblot analysis of KRAS. c Co-IP and immunoblot analysis of RAS and AGO2 upon EGF stimulation of HEK293 (wild-type KRAS ) cells expressing FLAG-AGO2 or ( d ) DLD-1 ( KRAS G13D ) cells in the presence or absence of erlotinib. e EGF stimulation and RAS co-IP analysis in HEK293 (wild-type KRAS ) and f MIA PaCa-2 ( KRAS G12C ) cells expressing FLAG-tagged AGO2 (wild-type or Y393F). IP of endogenous AGO2 upon H 2 O 2 treatment (4′), in H358 ( g ) and MIA PaCa-2 ( h ) cells harboring KRAS mutations, followed by immunoblot analysis of KRAS. i H 2 O 2 treatment and KRAS-AGO2 co-IP analysis in MIA PaCa-2 ( KRAS G12C ) cells expressing FLAG-tagged AGO2 (wild-type or Y393F). Numbers on the left of the immunoblots in this panel indicate protein molecular weights in kDa. j Left panels, Representative images of single target (RAS or AGO2) and RAS-AGO2 interaction PLA in wild-type RAS expressing PC3 cells across the indicated cell culture conditions. Right panels, Representative images of PLA to detect RAS-AGO2 interaction in wild-type RAS expressing MCF-7 (panel I) and oncogenic KRAS expressing HCT116 (panel II) and H358 (panel III) cells grown in the indicated culture conditions. PLA signals appear as red dots around DAPI stained nuclei in blue. Scale bar, 50 µm.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: Phosphorylation of AGO2 Y393 disrupts its interaction with KRAS. a Immunoprecipitation (IP) of endogenous AGO2 upon EGF stimulation (5′) in the indicated cancer cells expressing wild-type RAS followed by immunoblot analysis of KRAS. For MCF7 cells, endogenous co-IP analysis was performed using both AGO2 and KRAS-specific antibodies. For each cell line and panel in this figure, MAPK activation and levels of various proteins are shown as input blots. b IP of endogenous AGO2 upon EGF stimulation (5′), in the indicated cancer cells harboring different KRAS mutations, followed by immunoblot analysis of KRAS. c Co-IP and immunoblot analysis of RAS and AGO2 upon EGF stimulation of HEK293 (wild-type KRAS ) cells expressing FLAG-AGO2 or ( d ) DLD-1 ( KRAS G13D ) cells in the presence or absence of erlotinib. e EGF stimulation and RAS co-IP analysis in HEK293 (wild-type KRAS ) and f MIA PaCa-2 ( KRAS G12C ) cells expressing FLAG-tagged AGO2 (wild-type or Y393F). IP of endogenous AGO2 upon H 2 O 2 treatment (4′), in H358 ( g ) and MIA PaCa-2 ( h ) cells harboring KRAS mutations, followed by immunoblot analysis of KRAS. i H 2 O 2 treatment and KRAS-AGO2 co-IP analysis in MIA PaCa-2 ( KRAS G12C ) cells expressing FLAG-tagged AGO2 (wild-type or Y393F). Numbers on the left of the immunoblots in this panel indicate protein molecular weights in kDa. j Left panels, Representative images of single target (RAS or AGO2) and RAS-AGO2 interaction PLA in wild-type RAS expressing PC3 cells across the indicated cell culture conditions. Right panels, Representative images of PLA to detect RAS-AGO2 interaction in wild-type RAS expressing MCF-7 (panel I) and oncogenic KRAS expressing HCT116 (panel II) and H358 (panel III) cells grown in the indicated culture conditions. PLA signals appear as red dots around DAPI stained nuclei in blue. Scale bar, 50 µm.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Immunoprecipitation, Expressing, Co-Immunoprecipitation Assay, Activation Assay, Western Blot, Proximity Ligation Assay, Cell Culture, Staining

    AGO2 is essential for progression of precursor PanIN lesions to PDAC. a Schematic of the conditionally activated endogenous alleles of KRAS G12D and AGO2 used in the study to generate the AGO2 fl/fl ;KRAS G12D ;p48Cre experimental mice. b Representative images of H E and AGO2 IHC analysis of pancreata obtained from AGO2 +/+ ;p48Cre and AGO2 fl/fl ;p48Cre genotypes. Orange and black arrows indicate AGO2 expression in acinar cells and islets of Langerhans, respectively. Scale bar, 100 µm. c Representative H E and IHC analysis for AGO2 in pancreata obtained from 12-week old mice from the AGO2 +/+ ;KRAS G12D ;p48Cre and AGO2 fl/fl ;KRAS G12D ;p48Cre genotypes. Orange and black arrows indicate AGO2 staining in the PanIN and stromal regions, respectively. Scale bar, 100 µm. d Scatter plot showing the weight of pancreata obtained from 10 AGO2 +/+ ;KRAS G12D ;p48Cre , 17 AGO2 fl/+ ;KRAS G12D ;p48Cre , and 14 AGO2 fl/fl ;KRAS G12D ;p48Cre mice aged over 400 days. Two sided t-test was performed to determine the P value and error bars are mean values +/− SEM. e Histogram showing average number of early and late PanIN lesions observed in 11 mice each of AGO2 +/+ ;KRAS G12D ;p48Cre , AGO2 fl/+ ;KRAS G12D ;p48Cre , and AGO2 fl/fl ;KRAS G12D ;p48Cre genotypes at 400 days. The number of early/ late PanINs and PDAC within pancreatic sections from each animal were counted as a percentage. For AGO2 fl/fl ;KRAS G12D ;p48Cre mice, only lesions that do not express AGO2 have been included. f Kaplan–Meier curve for tumor-free survival of AGO2 +/+ ;KRAS G12D ;p48Cre , AGO2 fl/+ ;KRAS G12D ;p48Cre , and AGO2 fl/fl ; KRAS G12D ;p48Cre mice aged over 500 days. g Chart showing PDAC (within the pancreas), the different metastatic lesions, and abnormal pathologies (black boxes) observed in each mouse of the indicated genotypes aged over 500 days. Gray boxes in the AGO2 fl/fl ;KRAS G12D ;p48Cre group indicate abnormal pathology observed at the indicated site and are addressed in further detail in Supplementary Fig. 4 . The number of mice indicated in this figure represent biologically independent individuals.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: AGO2 is essential for progression of precursor PanIN lesions to PDAC. a Schematic of the conditionally activated endogenous alleles of KRAS G12D and AGO2 used in the study to generate the AGO2 fl/fl ;KRAS G12D ;p48Cre experimental mice. b Representative images of H E and AGO2 IHC analysis of pancreata obtained from AGO2 +/+ ;p48Cre and AGO2 fl/fl ;p48Cre genotypes. Orange and black arrows indicate AGO2 expression in acinar cells and islets of Langerhans, respectively. Scale bar, 100 µm. c Representative H E and IHC analysis for AGO2 in pancreata obtained from 12-week old mice from the AGO2 +/+ ;KRAS G12D ;p48Cre and AGO2 fl/fl ;KRAS G12D ;p48Cre genotypes. Orange and black arrows indicate AGO2 staining in the PanIN and stromal regions, respectively. Scale bar, 100 µm. d Scatter plot showing the weight of pancreata obtained from 10 AGO2 +/+ ;KRAS G12D ;p48Cre , 17 AGO2 fl/+ ;KRAS G12D ;p48Cre , and 14 AGO2 fl/fl ;KRAS G12D ;p48Cre mice aged over 400 days. Two sided t-test was performed to determine the P value and error bars are mean values +/− SEM. e Histogram showing average number of early and late PanIN lesions observed in 11 mice each of AGO2 +/+ ;KRAS G12D ;p48Cre , AGO2 fl/+ ;KRAS G12D ;p48Cre , and AGO2 fl/fl ;KRAS G12D ;p48Cre genotypes at 400 days. The number of early/ late PanINs and PDAC within pancreatic sections from each animal were counted as a percentage. For AGO2 fl/fl ;KRAS G12D ;p48Cre mice, only lesions that do not express AGO2 have been included. f Kaplan–Meier curve for tumor-free survival of AGO2 +/+ ;KRAS G12D ;p48Cre , AGO2 fl/+ ;KRAS G12D ;p48Cre , and AGO2 fl/fl ; KRAS G12D ;p48Cre mice aged over 500 days. g Chart showing PDAC (within the pancreas), the different metastatic lesions, and abnormal pathologies (black boxes) observed in each mouse of the indicated genotypes aged over 500 days. Gray boxes in the AGO2 fl/fl ;KRAS G12D ;p48Cre group indicate abnormal pathology observed at the indicated site and are addressed in further detail in Supplementary Fig. 4 . The number of mice indicated in this figure represent biologically independent individuals.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Mouse Assay, Immunohistochemistry, Expressing, Staining

    AGO2 loss prevents PanIN to PDAC progression through OIS. a β-galactosidase staining of pancreatic sections from AGO2 +/+ ; KRAS G12D ; p48Cre and AGO2 fl/fl ; KRAS G12D ; p48Cre mice at 70- and 500-day time points. Scale bar, 100 µm. b Scatter plot showing β-galactosidase staining in low grade PanINs. Data are from 47 PanINs from AGO2 +/+ ; KRAS G12D ; p48Cre and 98 PanINs from AGO2 fl/fl ; KRAS G12D ; p48Cre from four individual mice at the 70-day time point and 30 PanINs from three individual mice at 500-day time points. Intensity of staining and percent cells within 30 low grade PanINs were used to determine the senescence score = intensity × percent positive cells. p values were determined using a two sided t-test. Data are presented as mean values +/− SEM. c Immunoblot analysis of RAS-driven MAPK (indicated by pERK) and PI3K (indicated by pAKT) signaling from individual pancreata obtained from mice of the indicated genotypes, aged to 400 days. Numbers on the left indicate protein molecular weights in kDa. d Representative images of H E staining (left) and dual staining for β-galactosidase and phospho-ERK (right) in human pancreatic tissue with PanINs (representative staining of at least 10 PanINs from two patients). Scale bar, 40 µm. e Immune profile of lesions from the indicated genotypes. Ten consecutive fields (20x magnification) from four individual mice were assessed for the indicated IHC markers that distinguish immune cell populations. Significant p values are indicated and were determined using two tailed t -test. f Representative images of NK1.1-positive NK cells surrounding PanIN and PDAC lesions within the indicated genotypes. Scale bar, 50 µm. g Plot showing NK cell number in PanIN/PDAC lesions within the indicated genotypes. Pancreatic tissues from six mice were analyzed for NK1.1 IHC-positive NK cells. Two tailed t -test was used to determine p values. h Scatter plot showing peripheral and PanIN infiltrating NK cell count from PanINs in the indicated genotypes. Counts were obtained from 10 consecutive fields from six mice at ×20 magnification, and the indicated p values were determined using two tailed t -test. In relevant panels, data are presented as mean values +/− SEM.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: AGO2 loss prevents PanIN to PDAC progression through OIS. a β-galactosidase staining of pancreatic sections from AGO2 +/+ ; KRAS G12D ; p48Cre and AGO2 fl/fl ; KRAS G12D ; p48Cre mice at 70- and 500-day time points. Scale bar, 100 µm. b Scatter plot showing β-galactosidase staining in low grade PanINs. Data are from 47 PanINs from AGO2 +/+ ; KRAS G12D ; p48Cre and 98 PanINs from AGO2 fl/fl ; KRAS G12D ; p48Cre from four individual mice at the 70-day time point and 30 PanINs from three individual mice at 500-day time points. Intensity of staining and percent cells within 30 low grade PanINs were used to determine the senescence score = intensity × percent positive cells. p values were determined using a two sided t-test. Data are presented as mean values +/− SEM. c Immunoblot analysis of RAS-driven MAPK (indicated by pERK) and PI3K (indicated by pAKT) signaling from individual pancreata obtained from mice of the indicated genotypes, aged to 400 days. Numbers on the left indicate protein molecular weights in kDa. d Representative images of H E staining (left) and dual staining for β-galactosidase and phospho-ERK (right) in human pancreatic tissue with PanINs (representative staining of at least 10 PanINs from two patients). Scale bar, 40 µm. e Immune profile of lesions from the indicated genotypes. Ten consecutive fields (20x magnification) from four individual mice were assessed for the indicated IHC markers that distinguish immune cell populations. Significant p values are indicated and were determined using two tailed t -test. f Representative images of NK1.1-positive NK cells surrounding PanIN and PDAC lesions within the indicated genotypes. Scale bar, 50 µm. g Plot showing NK cell number in PanIN/PDAC lesions within the indicated genotypes. Pancreatic tissues from six mice were analyzed for NK1.1 IHC-positive NK cells. Two tailed t -test was used to determine p values. h Scatter plot showing peripheral and PanIN infiltrating NK cell count from PanINs in the indicated genotypes. Counts were obtained from 10 consecutive fields from six mice at ×20 magnification, and the indicated p values were determined using two tailed t -test. In relevant panels, data are presented as mean values +/− SEM.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Staining, Mouse Assay, Immunohistochemistry, Two Tailed Test, Cell Counting

    Increased AGO2 expression during mouse and human PDAC progression. a Representative images of AGO2 IHC analysis within an individual AGO2 +/+ ;KRAS G12D ; p48Cre mouse showing increased AGO2 expression in PDAC and metastasis compared with PanIN lesions. Arrows point to PanIN, PDAC, or metastatic PDAC in respective panels. In the metastasis panel, N = normal liver and T = tumor. Scale bar, 40 µm. b Representative images of IHC analysis for AGO2 expression in human PDAC progression showing elevated AGO2 protein expression in PDAC and metastatic tissue. Lower panels show higher magnifications of areas marked in the upper panels. Scale bars in the top and bottom panels are 200 and 80 µm, respectively. Arrows point to PanIN and PDAC. c Box and scatter plot showing AGO2 expression on a human tissue microarray (TMA) containing 44 human pancreatic tissue samples (24 precancerous, 14 PDAC, and six metastatic PDAC lesions), as determined by IHC analysis. Each sample was scored for intensity of stain and percent tumor cells staining for AGO2, and the final score = intensity × percent positive cells. p values were determined using a two sided t -test. Data are presented as mean values +/−SEM.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: Increased AGO2 expression during mouse and human PDAC progression. a Representative images of AGO2 IHC analysis within an individual AGO2 +/+ ;KRAS G12D ; p48Cre mouse showing increased AGO2 expression in PDAC and metastasis compared with PanIN lesions. Arrows point to PanIN, PDAC, or metastatic PDAC in respective panels. In the metastasis panel, N = normal liver and T = tumor. Scale bar, 40 µm. b Representative images of IHC analysis for AGO2 expression in human PDAC progression showing elevated AGO2 protein expression in PDAC and metastatic tissue. Lower panels show higher magnifications of areas marked in the upper panels. Scale bars in the top and bottom panels are 200 and 80 µm, respectively. Arrows point to PanIN and PDAC. c Box and scatter plot showing AGO2 expression on a human tissue microarray (TMA) containing 44 human pancreatic tissue samples (24 precancerous, 14 PDAC, and six metastatic PDAC lesions), as determined by IHC analysis. Each sample was scored for intensity of stain and percent tumor cells staining for AGO2, and the final score = intensity × percent positive cells. p values were determined using a two sided t -test. Data are presented as mean values +/−SEM.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Expressing, Immunohistochemistry, Microarray, Staining

    p53 loss bypasses requirement for AGO2 during PDAC progression. a Kaplan–Meier tumor-free survival of AGO2 +/+ ;KRAS G12D ;Trp53 fl/+ ;p48Cre , AGO 2 fl/+ ;KRAS G12D ;Trp53 fl/+ ;p48Cre , and AGO2 fl/fl ;KRAS G12D ;Trp53 fl/+ ;p48Cre mice. b Chart showing PDAC (within the pancreas), the different metastatic lesions, and abnormal pathologies (black boxes) observed in each mouse of the indicated genotypes. c Representative H E and AGO2 IHC in the indicated genotype. Scale bar, 100 µm.

    Journal: Nature Communications

    Article Title: An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

    doi: 10.1038/s41467-020-16309-2

    Figure Lengend Snippet: p53 loss bypasses requirement for AGO2 during PDAC progression. a Kaplan–Meier tumor-free survival of AGO2 +/+ ;KRAS G12D ;Trp53 fl/+ ;p48Cre , AGO 2 fl/+ ;KRAS G12D ;Trp53 fl/+ ;p48Cre , and AGO2 fl/fl ;KRAS G12D ;Trp53 fl/+ ;p48Cre mice. b Chart showing PDAC (within the pancreas), the different metastatic lesions, and abnormal pathologies (black boxes) observed in each mouse of the indicated genotypes. c Representative H E and AGO2 IHC in the indicated genotype. Scale bar, 100 µm.

    Article Snippet: AGO2 was purchased from Sino Biologicals.

    Techniques: Mouse Assay, Immunohistochemistry