Wilms' tumor 1 suppressor gene mediates antiestrogen resistance via down-regulation of estrogen receptor-alpha expression in breast cancer cells.

Molecular Cancer Research : MCR
Youqi HanMark D Minden

Abstract

The antiestrogen tamoxifen has been used in the treatment of hormone-responsive breast cancer for over a decade. The loss of estrogen receptor (ER) expression is the most common mechanism for de novo antiestrogen resistance. Wilms' tumor 1 suppressor gene (WT1) is a clinically useful marker that is associated with poor prognosis in breast cancer patients; its high level expression is frequently observed in cases of breast cancer that are estrogen and progesterone receptor negative. The lack of expression of these receptors is characteristic of tumor cells that are not responsive to hormonal manipulation. To determine whether there is a linkage between WT1 expression and antiestrogen resistance in breast cancer cells, we studied the effect of WT1 on tamoxifen responsiveness in ERalpha-positive MCF-7 cells. We found that overexpression of WT1 in MCF-7 markedly abrogated tamoxifen-induced cell apoptosis and 17beta-estradiol (E(2))-mediated cell proliferation. The expressions of ERalpha and its downstream target genes were significantly repressed following overexpression of WT1, whereas the down-regulation of WT1 by WT1 shRNA could enhance ERalpha expression and the sensitivity to tamoxifen treatment in ERalpha-negative MDA468 and ...Continue Reading

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D A HaberD E Housman
Jan 1, 1994·Breast Cancer Research and Treatment·R ClarkeN Brunner
Apr 1, 1995·Molecular and Cellular Biology·E C deConinckR J Weigel
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·G B SilbersteinC W Daniel
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·C M PerouD Botstein
Mar 10, 2001·Experimental Cell Research·S B Lee, D A Haber
Jul 14, 2001·Nucleic Acids Research·C M Klinge
Oct 12, 2001·Gene·V ScharnhorstA G Jochemsen
Oct 12, 2001·Apoptosis : an International Journal on Programmed Cell Death·S Mandlekar, A N Kong
Mar 29, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·David J RickardThomas C Spelsberg
Jul 20, 2002·Biochemical and Biophysical Research Communications·Pablo Zapata-BenavidesAna M Tari
Dec 20, 2002·The New England Journal of Medicine·Marc J van de VijverRené Bernards
Jun 7, 2003·Endocrine-related Cancer·H RochefortM Garcia
Oct 25, 2003·Oncogene·Robert ClarkeLeena A Hilakivi-Clarke
Nov 14, 2003·Cancer Biology & Therapy·Peter D Adams, Paul Cairns
Mar 24, 2004·Trends in Endocrinology and Metabolism : TEM·Christian J GruberJohannes C Huber
Apr 8, 2004·Neoplasia : an International Journal for Oncology Research·Daniel R RhodesArul M Chinnaiyan
Aug 3, 2004·Oncogene·Youqi HanMark D Minden
Nov 13, 2004·Breast Cancer Research : BCR·D Craig AllredDaniel Medina
Jun 1, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M MacalusoA Giordano
Jul 16, 2005·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Angiolo GadducciAndrea Riccardo Genazzani

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Citations

Oct 9, 2012·Human Molecular Genetics·Marianna SzemesKarim Malik
Jun 28, 2020·Hormones & Cancer·David K LungElaine T Alarid
Jun 14, 2014·The Biochemical Journal·Eneda Toska, Stefan G E Roberts
Oct 9, 2013·Biochemical and Biophysical Research Communications·Yu ZhangPeter C K Leung
Nov 22, 2011·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mei Lan TanTengku Sifzizul Tengku Muhammad

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