Journal: Breast Cancer Research : BCR

Article Title: Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer

doi: 10.1186/s13058-018-0983-1

Figure Lengend Snippet: Simplified schematic diagram of the pathways described in this study. a Growth factor signalling (IGFR and ERBB) leads to activation of PI3K and phosphorylation of AKT. AKT inhibits TCS1/2, resulting in upregulation of mTORC1. In parallel, mTORC1 can also be upregulated by the RAS-RAF-MEK-ERK signalling pathway. ERK phosphorylates and inactivates TCS2 also leading to mTORC1 activation. S6 K1 activity increases as a result of mTORC1 activation. S6 K1 suppresses mTORC2 and IRS1. ER is also a target of S6 K1 leading to phosphorylation of serine 167. b Inhibition of mTORC1 with everolimus suppresses S6 K1 removing the negative feedback loop causing a rise in IRS1 and AKT activity via loss of suppression on mTORC2. Increased AKT activity suppresses TCS1/2 and increases expression of growth factor receptors (ERBB2/3) enhancing RAS-RAF-ERK signalling. c The dual blockade of ERBBs (neratinib) and mTORC1 signalling (everolimus) may suppress the two feedback loops described in b . Yellow shows normal mTORC signalling cascade; blue represents activated proteins; red represents inhibited proteins; dotted lines show loss of normal feedback loops

Article Snippet: Primary antibodies against phospho-EGFR tyr1068 (CST-3777), total-EGFR (CST-2232), phospho-ERBB2 tyr1248 (CST-2247), phospho-ERBB3 tyr1222 (CST-4784), total-ERK1/2 (CST-9102), phospho-AKT ser473 (CST-9271), total-AKT (CST-9272), phospho-S6 ser240/244 (CST-5364), total-S6 (CST-2217), phospho-ER ser167 (CST-5587), phospho-Rb ser807/811 (CST-8516), CDK4 (CST-2901), and cyclinD1 (CST-2922) were purchased from Cell Signaling, Inc.; total-ERBB3 (sc-415), ER-alpha (sc-8002, F-10), and PARP (sc-8007) were purchased from Santa Cruz; phospho-ERK1/2 and α-tubulin (T-9026) were obtained from Sigma; and total-ERBB2 was obtained from Millipore.

Techniques: Activation Assay, Activity Assay, Inhibition, Expressing

Journal: Breast Cancer Research : BCR

Article Title: Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations

doi: 10.1186/bcr2625

Figure Lengend Snippet: Effect of treatment of BT474 cells on receptor signaling . Effect of all- trans retinoic acid (atRA), trastuzumab or the combination on HER2 expression level and activity, on AKT expression level and activity, on mitogen-activated protein kinase (MAPK) expression level and activity, and on expression levels of retinoic acid receptor (RAR)α, RARβ, retinoid X receptor (RXR)α and RXRβ in BT474 cells. Drugs used at indicated concentrations. pHER2, pMAPK and pAKT, phospho-HER2, phospho-MAPK and phospho-AKT, respectively.

Article Snippet: Antibody to phospho-HER2 (Tyr-1248) (c-erbB-2/HER-2/ neu phospho-specific Ab-18) was from NeoMarkers (Fremont, CA, USA) and antibody to actin was from Sigma (St Louis, MO, USA).

Techniques: Expressing, Activity Assay