Cancer Research TCM Europe  EMT and Cancer Progression and Treatment
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Cancer Research 68, 4910, June 15, 2008. doi: 10.1158/0008-5472.CAN-08-0303
© 2008 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Masri, S.
Right arrow Articles by Chen, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Masri, S.
Right arrow Articles by Chen, S.

Endocrinology

Genome-Wide Analysis of Aromatase Inhibitor-Resistant, Tamoxifen-Resistant, and Long-Term Estrogen-Deprived Cells Reveals a Role for Estrogen Receptor

Selma Masri1, Sheryl Phung1, Xin Wang1, Xiwei Wu2, Yate-Ching Yuan2, Lawrence Wagman3 and Shiuan Chen1

1 Department of Surgical Research, 2 Division of Information Sciences, and 3 Department of General Oncologic Surgery, Beckman Research Institute of the City of Hope, Duarte, California

Requests for reprints: Shiuan Chen, Department of Surgical Research, Beckman Research Institute of the City of Hope, 1500 E Duarte Road, Duarte, CA 91010. Phone: 626-359-8111, ext. 63454; Fax: 626-301-8972; E-mail: schen{at}coh.org.

Key Words: endocrine resistance • aromatase inhibitors • estrogen receptor • microarray

Acquired resistance to either tamoxifen or aromatase inhibitors (AI) develops after prolonged treatment in a majority of hormone-responsive breast cancers. In an attempt to further elucidate mechanisms of acquired resistance to AIs, MCF-7aro cells resistant to letrozole (T+LET R), anastrozole (T+ANA R), and exemestane (T+EXE R), as well as long-term estrogen deprived (LTEDaro) and tamoxifen-resistant (T+TAM R) lines were generated. This is the first complete panel of endocrine therapy–resistant cell lines, which were generated as multiple independent biological replicates for unbiased genome-wide analysis using affymetrix microarrays. Although similarities are apparent, microarray results clearly show gene signatures unique to AI-resistance were inherently different from LTEDaro and T+TAM R gene expression profiles. Based on hierarchical clustering, unique estrogen-responsive gene signatures vary depending on cell line, with some genes up-regulated in all lines versus other genes up-regulated only in the AI-resistant lines. Characterization of these resistant lines showed that LTEDaro, T+LET R, and T+ANA R cells contained a constitutively active estrogen receptor (ER){alpha} that does not require estrogen for activation. This ligand-independent activation of ER was not observed in the parental cells, as well as T+EXE R and T+TAM R cells. Further characterization of these resistant lines was performed using cell cycle analysis, immunofluorescence experiments to visualize ER subcellular localization, as well as cross-resistance studies to determine second-line inhibitor response. Using this well-defined model system, our studies provide important information regarding differences in resistance mechanisms to AIs, TAM, and LTEDaro, which are critical in overcoming resistance when treating hormone-responsive breast cancers. [Cancer Res 2008;68(12):4910–8]




This article has been cited by other articles:


Home page
Cancer Res.Home page
K. McCune, P. Bhat-Nakshatri, M. A. Thorat, K. P. Nephew, S. Badve, and H. Nakshatri
Prognosis of Hormone-Dependent Breast Cancers: Implications of the Presence of Dysfunctional Transcriptional Networks Activated by Insulin via the Immune Transcription Factor T-bet
Cancer Res., January 15, 2010; 70(2): 685 - 696.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
C. Wong and S. Chen
Heat Shock Protein 90 Inhibitors: New Mode of Therapy to Overcome Endocrine Resistance
Cancer Res., November 15, 2009; 69(22): 8670 - 8677.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
I. Barone, Y. Cui, M. H. Herynk, A. Corona-Rodriguez, C. Giordano, J. Selever, A. Beyer, S. Ando, and S. A.W. Fuqua
Expression of the K303R Estrogen Receptor-{alpha} Breast Cancer Mutation Induces Resistance to an Aromatase Inhibitor via Addiction to the PI3K/Akt Kinase Pathway
Cancer Res., June 1, 2009; 69(11): 4724 - 4732.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.