Clinical trials have highlighted the importance of aromatase inhibitors in the treatment of breast cancer. Yet, as with all prolonged drug therapy, resistance does develop via a currently unknown mechanism. This lab hypothesizes that resistance to aromatase inhibitors does entail an alternate signaling pathway that allows cells to adapt to the presence of the inhibitor, but still undergo normal cell proliferation. To address this question, this lab has generated MCF-7aro (aromatase overexpressed) breast cancer cell lines that are resistant to aromatase inhibitors and the anti-estrogen tamoxifen. 1. To investigate candidate genes involved in resistance to aromatase inhibitors, this lab intends to perform microarray analysis of the MCF-7aro resistant cell lines. 2. To better understand how genes identified by microarray are involved in resistance to aromatase inhibitors, further mechanistic studies will be done, by gene overexpression or knockdown in cell culture and analysis of activated signal transduction pathways. This project has critical clinical implications in that the effective treatment of breast carcinomas does rely on understanding drug-resistance at the molecular level. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA123691-03
Application #
7480377
Study Section
Special Emphasis Panel (ZRG1-IMM-L (29))
Program Officer
Bini, Alessandra M
Project Start
2006-08-28
Project End
2009-06-30
Budget Start
2008-08-28
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$23,750
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
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Masri, Selma; Liu, Zheng; Phung, Sheryl et al. (2010) The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells. Breast Cancer Res Treat 124:89-99
Masri, Selma; Lui, Ki; Phung, Sheryl et al. (2009) Characterization of the weak estrogen receptor alpha agonistic activity of exemestane. Breast Cancer Res Treat 116:461-70
Wang, Xin; Masri, Selma; Phung, Sheryl et al. (2008) The role of amphiregulin in exemestane-resistant breast cancer cells: evidence of an autocrine loop. Cancer Res 68:2259-65
Masri, Selma; Phung, Sheryl; Wang, Xin et al. (2008) Genome-wide analysis of aromatase inhibitor-resistant, tamoxifen-resistant, and long-term estrogen-deprived cells reveals a role for estrogen receptor. Cancer Res 68:4910-8
Chen, Shiuan; Masri, Selma; Hong, Yanyan et al. (2007) New experimental models for aromatase inhibitor resistance. J Steroid Biochem Mol Biol 106:8-15