Release of HER2 repression of trefoil factor 3 (TFF3) expression mediates trastuzumab resistance in HER2+/ER+ mammary carcinoma

Oncotarget
Qing-Yun ChongPeter E Lobie

Abstract

HER2+/ER+ breast cancer, a subset of the luminal B subtype, makes up approximately 10% of all breast cancers. The bidirectional crosstalk between HER2 and estrogen receptor (ER) in HER2+/ER+ breast cancer contributes to resistance towards both anti-estrogens and HER2-targeted therapies. TFF3 promotes breast cancer progression and has been implicated in anti-estrogen resistance in breast cancer. Herein, we investigated the cross-regulation between HER2 and estrogen-responsive TFF3, and the role of TFF3 in mediating trastuzumab resistance in HER2+/ER+ breast cancer. TFF3 expression was decreased by HER2 activation, and increased by inhibition of HER2 with trastuzumab in HER2+/ER+ breast cancer cells, partially in an ERα-independent manner. In contrast, the forced expression of TFF3 activated the entire HER family of receptor tyrosine kinases (HER1-4). Hence, HER2 negatively regulates its own signalling through the transcriptional repression of TFF3, while trastuzumab inhibition of HER2 results in increased TFF3 expression to compensate for the loss of HER2 signalling. In HER2+/ER+ breast cancer cells with acquired trastuzumab resistance, TFF3 expression was markedly upregulated and associated with a corresponding decrease in HER ...Continue Reading

References

Sep 4, 1996·International Journal of Cancer. Journal International Du Cancer·B Ogretmen, A R Safa
Feb 3, 1998·Cellular and Molecular Life Sciences : CMLS·L Thim
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·L N KlapperY Yarden
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·D R TaupinD K Podolsky
May 16, 2000·The Journal of Endocrinology·A StoicaM B Martin
Aug 5, 2000·Biochemical and Biophysical Research Communications·Y H ChenX D Tan
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Jul 21, 2001·Molecular Endocrinology·A S OhD El-Ashry
Dec 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Harold J BursteinEric P Winer
Jan 17, 2003·Journal of the National Cancer Institute·Gottfried KonecnyDennis J Slamon
Jul 30, 2003·Cancer Metastasis Reviews·Patrick C MaRavi Salgia
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Douglas Taupin, Daniel K Podolsky
Dec 4, 2003·International Journal of Cancer. Journal International Du Cancer·Yuhong LuMichael Pollak
Feb 24, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Athanassios ArgirisMichael P DiGiovanna
Jun 5, 2004·Peptides·Shahin EmamiChristian Gespach
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberto GennariAlberto Costa
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michele MilellaGabriella Zupi
Aug 20, 2005·International Journal of Gastrointestinal Cancer·Thaer KhouryDongfeng Tan
Sep 15, 2005·International Journal of Cancer. Journal International Du Cancer·Gernot HudelistChristian F Singer
Dec 24, 2005·Cellular and Molecular Life Sciences : CMLS·W Hoffmann
Mar 22, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Judith HurleyDennis J Slamon
May 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Wenle XiaNeil L Spector
Feb 24, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lyndsay N HarrisEric P Winer
Jul 27, 2007·Journal of Cell Science·Shujie YangBridget S Wilson
Aug 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christoph A RitterCarlos L Arteaga
Dec 7, 2007·Trends in Endocrinology and Metabolism : TEM·Jo K PerryPeter E Lobie
Dec 23, 2008·Cellular and Molecular Life Sciences : CMLS·S Kjellev
Dec 25, 2008·Nature Clinical Practice. Oncology·Gabriella MarianiLuca Gianni
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alessandra MagnificoElda Tagliabue

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Citations

Sep 21, 2018·American Society of Clinical Oncology Educational Book·Mark D PegramStacy L Moulder
Mar 18, 2021·Future Oncology·Charlene KayArran K Turnbull

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Methods Mentioned

BETA
transfection
Assay
PCR
electrophoresis

Software Mentioned

ImageJ
GraphPad Prism

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