Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity.

Oncogene
Ines BaroneS A W Fuqua

Abstract

We earlier identified a lysine to arginine transition at residue 303 (K303R) in estrogen receptor alpha (ERalpha) in invasive breast cancers, which confers resistance to the aromatase inhibitor (AI) anastrozole (Ana) when expressed in MCF-7 breast cancer cells. Here, we show that AI resistance arises through an enhanced cross talk of the insulin-like growth factor receptor-1 (IGF-1R)/insulin receptor substrate (IRS)-1/Akt pathway with ERalpha, and the serine (S) residue 305 adjacent to the K303R mutation has a key function in mediating this cross talk. The ERalpha S305 residue is an important site that modifies response to tamoxifen; thus, we questioned whether this site could also influence AI response. We generated stable transfectants-expressing wild-type, K303R ERalpha or a double K303R/S305A mutant receptor, and found that the AI-resistant phenotype associated with expression of the K303R mutation was dependent on activation of S305 within the receptor. Ana significantly reduced growth in K303R/S305A-expressing cells. Preventing S305 phosphorylation with a blocking peptide inhibited IGF-1R/IRS-1/Akt activation and also restored AI sensitivity. Our data suggest that the K303R mutation and the S305 ERalpha residue may be a n...Continue Reading

References

Jan 1, 1993·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·L R WisemanB R Westley
Jan 1, 1993·Breast Cancer Research and Treatment·C A EncarnaciónC K Osborne
Dec 1, 1995·Current Opinion in Cell Biology·G I EvanE Harrington
Apr 3, 1999·International Journal of Cancer. Journal International Du Cancer·M SalernoE Surmacz
May 18, 2001·Nature·P Blume-Jensen, T Hunter
Dec 12, 2002·Science's STKE : Signal Transduction Knowledge Environment·Brendan D Manning, Lewis C Cantley
Nov 15, 2003·The Journal of Biological Chemistry·Deepali SachdevDouglas Yee
Nov 26, 2003·Biochimica Et Biophysica Acta·Hanna Ksiezak-RedingGiulio M Pasinetti
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rachel SchiffC Kent Osborne
Feb 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Robert X SongRichard J Santen
Dec 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Irina U AgoulnikDirk G Kieback
Jan 11, 2005·The Journal of Pathology·E FoulstoneA B Hassan
Jul 19, 2005·The Journal of Steroid Biochemistry and Molecular Biology·R J SantenL Berstein
Sep 5, 2006·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H Faus, B Haendler
Jan 24, 2007·Molecular Cancer Therapeutics·Deepali Sachdev, Douglas Yee
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Matthew H HerynkSuzanne A W Fuqua
Jul 3, 2007·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Suresh K Rayala, Rakesh Kumar
Oct 9, 2007·Biochemical and Biophysical Research Communications·Danielle Renee FontenotRakesh Kumar
Jan 29, 2008·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Hiroo NakajimaSei-ichi Tanuma
May 13, 2008·Molecular Cell·Krithika SubramanianPaula M Vertino
Aug 30, 2008·Molecular and Cellular Endocrinology·Robin TharakanSohaib Khan

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Citations

Jun 1, 2012·Archives of Toxicology·Katherine A Burns, Kenneth S Korach
Jul 11, 2013·Trends in Endocrinology and Metabolism : TEM·Lindsey S Treviño, Nancy L Weigel
Mar 31, 2011·Journal of the National Cancer Institute·Ines BaroneSuzanne A W Fuqua
Feb 4, 2014·Breast Cancer Research and Treatment·Suzanne A W FuquaYassine Rechoum
Nov 6, 2013·Biochimica Et Biophysica Acta·Yousef HawsawiJames Beattie
Jul 25, 2014·Endocrine-related Cancer·M Christine BruceLeigh C Murphy
Jul 1, 2015·Nature Reviews. Clinical Oncology·Rinath JeselsohnRachel Schiff
Oct 2, 2013·The Lancet Oncology·Michel van KruchtenGeke A P Hospers
Aug 17, 2012·Cell Cycle·Marina K Holz
May 15, 2016·Breast Cancer Research and Treatment·Luca GelsominoSuzanne A W Fuqua
May 8, 2018·Hormones & Cancer·Sasha M PejerreySuzanne A W Fuqua
Jun 18, 2011·Endocrine Reviews·Muriel Le RomancerLaura Corbo
Jul 19, 2019·Cancer·Derek DustinSuzanne A W Fuqua
Jun 21, 2019·International Journal of Molecular Sciences·Kumaraswamy Naidu ChitralaSuneetha Yeguvapalli
Mar 12, 2017·Breast Cancer Research and Treatment·Takehiro YanagawaShinzaburo Noguchi
Nov 22, 2019·Frontiers in Endocrinology·Prathibha RanganathanSughosha Nambiar
Aug 23, 2020·International Journal of Molecular Sciences·Giuseppina AugimeriStefania Catalano
Mar 23, 2012·Nuclear Receptor Signaling·Muralidharan AnbalaganBrian G Rowan
Sep 17, 2020·Cells·Sarah A JeffreysTherese M Becker
Mar 30, 2021·Frontiers in Oncology·Kevin Roarty, Gloria V Echeverria
May 18, 2021·Molecular and Cellular Endocrinology·Fahmida RashaKevin Pruitt
Sep 25, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Ines BaroneSebastiano Andò

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Methods Mentioned

BETA
coimmunoprecipitation
immunoprecipitation
acetylation

Software Mentioned

NETPHOS
GraphPad
GraphPAD Prism5

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