Article title: PI3K independent activation of mTORC1 as a target in lapatinib-resistant ERBB2+ breast cancer cells Journal: Breast Cancer Research and.

Slides:

Advertisements

Similar presentations

Student Research Interest HER2 Receptor Signaling in Breast Cancer Cells Marc Y. Fink Biomedical Sciences LIU-Post.

Advertisements

Supplementary Materials and Methods Real-time RT-PCR Genomic DNA was isolated from washed cell pellets of eight biliary tract cancer cell lines (SNU-245,

Article Title: AKT-aro and HER2-aro, models for de novo resistance to aromatase inhibitors; molecular characterization and inhibitor response studies Journal.

Supplementary Figure S1 Inhibition of AKT and S6 phosphorylation. After 4 h treatment with 1 µM of GDC-0941, EVSA-T parental, resistant Clone1, Clone2,

High molecular weight hyaluronic acid regulates osteoclast formation by inhibiting receptor activator of NF-κB ligand through Rho kinase W. Ariyoshi,

Figure 6. Effect of Withaferin A (WA) treatment on leptin-induced signaling in breast cancer cells. A) Immunoblotting for pSTAT3 (Tyr705), total STAT3,

A conditional feedback loop regulates Ras activity through EphA2

Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy Flavia.

Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy Dina Chelouche-Lev, Claudia P. Miller, Carmen.

Volume 30, Issue 3, Pages (September 2016)

Figure 5 ISOX and vorinostat partially restore splicing pattern in DM1 patient-derived fibroblasts. (A) ISOX and vorinostat partially rescue mis-splicing.

Volume 16, Issue 3, Pages e4 (March 2014)

High molecular weight hyaluronic acid regulates osteoclast formation by inhibiting receptor activator of NF-κB ligand through Rho kinase W. Ariyoshi,

AZD9291 inhibits EGFR phosphorylation and downstream signaling in murine models of EGFRT790M-resistant lung cancer. AZD9291 inhibits EGFR phosphorylation.

Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2–Amplified Gastric Cancer Patient–Derived Cell Model Jiryeon Jang, Hee Kyung Kim,

Volume 133, Issue 2, Pages (August 2007)

Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe–Based Single-

Volume 26, Issue 2, Pages (August 2014)

Rafal Dziadziuszko, MD, PhD, Anh T

A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI- 258) and its Therapeutic Implications Shalini S. Yadav, Jinyi.

KIND1 Loss Sensitizes Keratinocytes to UV-Induced Inflammatory Response and DNA Damage Xiaoling Zhang, Suju Luo, Joseph Wu, Long Zhang, Wen-hui Wang,

Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression by Takahiro Nemoto, Hisae Hori, Masataka.

Volume 55, Issue 1, Pages (July 2014)

Supplementary Table 1 Sequences of the primer used for q-PCR analysis

A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling

Volume 67, Issue 3, Pages e4 (August 2017)

Supplemental Information

MET Increases the Sensitivity of Gefitinib-Resistant Cells to SN-38, an Active Metabolite of Irinotecan, by Up-Regulating the Topoisomerase I Activity

Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy Flavia.

Volume 19, Issue 1, Pages (January 2011)

Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal Differentiation Nan-Lin Wu, Duen-Yi Huang, Li-Fang Wang, Reiji Kannagi,

Akio Horiguchi, Mototsugu Oya, Ken Marumo, Masaru Murai

Yongli Bai, Chun Yang, Kathrin Hu, Chris Elly, Yun-Cai Liu

A Novel Mass Spectrometry–Based Assay for Diagnosis of EML4-ALK–Positive Non– Small Cell Lung Cancer Kazuko Sakai, PhD, Isamu Okamoto, MD, PhD, Ken Takezawa,

Lovastatin Sensitizes Lung Cancer Cells to Ionizing Radiation: Modulation of Molecular Pathways of Radioresistance and Tumor Suppression Toran Sanli,

Downregulation of Melanin Synthesis by Haginin A and Its Application to In Vivo Lightening Model Jin Hee Kim, Seung Hwa Baek, Dong Hyun Kim, Tae Young.

1,25-dihydroxyvitamin D3 inhibits renal interstitial myofibroblast activation by inducing hepatocyte growth factor expression Yingjian Li, Bradley C.

Supplementary Figure 1. Structure of amlexanox

Stratifin-Induced Matrix Metalloproteinase-1 in Fibroblast Is Mediated by c-fos and p38 Mitogen-Activated Protein Kinase Activation Eugene Lam, Runhangiz.

Volume 30, Issue 3, Pages (September 2016)

Kellie J. White, Vincent J. Maffei, Marvin Newton-West, Robert A

Volume 20, Issue 4, Pages (October 2011)

Amplification and Overexpression of the EMS 1 Oncogene, a Possible Prognostic Marker, in Human Hepatocellular Carcinoma Bao-Zhu Yuan, Xiaoling Zhou,

Chi-Hyun Park, Youngji Moon, Chung Min Shin, Jin Ho Chung

Volume 26, Issue 2, Pages (August 2014)

Volume 10, Issue 3, Pages (September 2006)

Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37 Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young.

A conditional feedback loop regulates Ras activity through EphA2

Role of HER2 in mediating acquired resistance to EGFR inhibition.

RNA Polymerase II Activity of Type 3 Pol III Promoters

Cellular 5′-3′ mRNA Exonuclease Xrn1 Controls Double-Stranded RNA Accumulation and Anti-Viral Responses Hannah M. Burgess, Ian Mohr Cell Host & Microbe

MET Increases the Sensitivity of Gefitinib-Resistant Cells to SN-38, an Active Metabolite of Irinotecan, by Up-Regulating the Topoisomerase I Activity

Inhibition of the Epidermal Growth Factor Receptor Suppresses Telomerase Activity in HSC-1 Human Cutaneous Squamous Cell Carcinoma Cells Arief Budiyanto,

The role of SRC-C3G-RAP1 signaling in transformation induced by CRKL

Volume 39, Issue 3, Pages (August 2010)

High-level clonal amplification of FGFR2 predicts for sensitivity to FGFR inhibitor. High-level clonal amplification of FGFR2 predicts for sensitivity.

Volume 67, Issue 3, Pages e4 (August 2017)

Acquired BRAF Rearrangements Induce Secondary Resistance to EGFR therapy in EGFR-Mutated Lung Cancers Morana Vojnic, MD, Daisuke Kubota, MD, PhD, Christopher.

Volume 55, Issue 1, Pages (July 2014)

Volume 17, Issue 1, Pages (January 2010)

A, GP and GR epithelial tumor cells are equally responsive to gefitinib. A, GP and GR epithelial tumor cells are equally responsive to gefitinib. Equal.

Down-regulation of the erbB-2 receptor by trastuzumab decreases Akt kinase activation but not MAPK activation. Down-regulation of the erbB-2 receptor by.

MET amplification is selected in KRAS wild-type colorectal cancer samples from patients who developed resistance to anti-EGFR treatment. MET amplification.

ERK reactivation following EGFR TKI treatment.

Dysregulated NF-κB activation in Il1r8+/+/lpr and Il1r8−/−/lpr mice.

Cell lines with aberrant expression of NRG1 are exquisitely sensitive to downregulation of ERBB3 signaling. Cell lines with aberrant expression of NRG1.

Changes in signal transduction pathway induced by gefitinib.

Effect of SFN on the total activity and protein expression of HDACs in JB6 P+ cells. Effect of SFN on the total activity and protein expression of HDACs.

Presentation transcript:

Article title: PI3K independent activation of mTORC1 as a target in lapatinib-resistant ERBB2+ breast cancer cells Journal: Breast Cancer Research and Treatment Authors: Anna-Maria Jegg1, Toby M. Ward1, Elizabeth Iorns3, Nicholas Hoe4, JinYao Zhou4, Xiaofei Liu1, Sharat Singh4, Ralf Landgraf2 and Mark D. Pegram1 1Division of Hematology and Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL 33136 2Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136 3Science Exchange, Inc. Palo Alto, CA 94301 4Prometheus Laboratories, San Diego, CA 92121 Corresponding author: Mark D. Pegram; mpegram@stanford.edu

A B C Supplementary Figure 1 SK-lapR SKBR3 SK-lapR 2.6μM lap - + - + - DMSO lapatinib AZD0530 AZD + lap p-SRC 48h 24h 48h 24h 48h 24h 48h 24h 48h p-SRCY416 SRC actin p-ERK ERK C SK-lapR ERa - DMSO lapatinib PD325901 PD + lap 48h 24h 48h 24h 48h 24h 48h 24h 48h actin p-ERK1/2T202/T204 actin Supplementary Figure 1 Constitutively active SRC and ERK1/2 signaling does not mediate resistance to lapatinib in SK-lapR cells. a: Phospho-SRC levels are increased in SK-lapR cells, and lapatinib does not inhibit ERK1/2 phosphorylation in SK-lapR cells. SKBR3 and SK-lapR cells were treated for 24h with 2.6μM lapatinib (+) or DMSO (-) and cell lysates were analyzed by immunoblot analysis using indicated antibodies. b, c: Inhibition of SRC with 1μM AZD0530 (B) and ERK1/2 with 1μM PD325901 (C) does not re-sensitize SK-lapR cells to lapatinib. SK-lapR cells were treated with DMSO, 2.6μM lapatinib, 1μM AZD0530 (B) and 1μM PD325901 (C), and combinations of drugs for 4 days. Cell numbers were determined by cell count on day 0 (before treatment) and day 4. Cell proliferation is plotted as fold increase relative to the cell number on day 0 [mean ± SD of triplicate experiments]. Inhibition of SRC with AZD0530 and ERK1/2 respectively after 24h and 48h was confirmed by immunoblot analysis

Relative mRNA expression Supplementary Figure 2 A B SKBR3 SK-lapR 25 EGFR mRNA 20 15 Relative mRNA expression [fold increase] 10 5 SKBR3 SK-lapR EGFR/CEN ratio: 0.99 = no amplification (346/348 in 50 cells) EGFR/CEN ratio: 1.046 = no amplification (383/366) in 50 cells) Supplementary Figure 2: Increased EGFR gene expression in SK-lapR cells is not mediated by EGFR gene amplification. a: Quantitative PCR (qPCR) analysis of EGFR mRNA expression in SKBR3 and SK-lapR cells. cDNAs were analyzed using primers for EGFR as well as GAPDH for normalization. Data is shown as fold increase relative to EGFR expression in SKBR3 cells. b: Representative images for EGFR- fluorescence in situ hybridization (FISH) in SKBR3 and SK-lapR cells. Formalin fixed, agarose embedded cell pellets were prepared with SKBR3 and SK-lapR cells and small sections were analyzed by FISH with EGFR and centromer 7 specific DNA probes. EGFR gene copies (red) and number of chromosome 7 centromeres (CEN; green) were counted in 200 cells/ cell line and EGFR amplification was determined by EGFR/CEN ratio. No amplification of EGFR was detected in SKBR3 or SK-lapR cells.