Abstract

The long-term objectives of this project are to understand the role of in situ aromatase in breast tumors, and to generate information useful for controlling estrogen biosynthesis in breast cancer patients. Aromatase expression in breast tumor specimens will be evaluated by Southern and DNA slot blot analysis, polymerase chain reactions (PCR), immunohistochemistry, and enzyme activity measurement. The expression level will be correlated with estrogen and progesterone hormone receptor status and several clinico-pathological parameters. Such a study will shed light on the clinical significance of in situ aromatization. Site-directed mutagenesis and active site-labeling experiments will be applied to generate structural information at the active site region of aromatase that can be used in the design of more effective aromatase inhibitors for the treatment of breast cancer. The regulatory mechanism of aromatase expression in breast cancer cells and other estrogen producing cells by hormones, and other reagents will also be investigated. Information generated from this investigation will be very important for further refinements of hormone therapy for breast cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044735-06
Application #
2091587
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1988-07-01
Project End
1995-12-31
Budget Start
1994-04-01
Budget End
1995-12-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010

  Publications

Wang, Yuanzhong; Zhou, Dujin; Phung, Sheryl et al. (2017) SGK3 sustains ER? signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis. Proc Natl Acad Sci U S A 114:E1500-E1508
Kanaya, Noriko; Somlo, George; Wu, Jun et al. (2017) Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. J Steroid Biochem Mol Biol 170:65-74
Chan, Hei Jason; Petrossian, Karineh; Chen, Shiuan (2016) Structural and functional characterization of aromatase, estrogen receptor, and their genes in endocrine-responsive and -resistant breast cancer cells. J Steroid Biochem Mol Biol 161:73-83
Chan, Hei Jason; Li, Haiqing; Liu, Zheng et al. (2015) SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients. Oncotarget 6:25815-27
Wang, Yuanzhong; Zhou, Dujin; Chen, Shiuan (2014) SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1. Mol Endocrinol 28:935-48
Wang, Yuanzhong; Xu, Wanping; Zhou, Dujin et al. (2014) Coordinated regulation of serum- and glucocorticoid-inducible kinase 3 by a C-terminal hydrophobic motif and Hsp90-Cdc37 chaperone complex. J Biol Chem 289:4815-26
Wong, Cynthie; Wang, Xin; Smith, David et al. (2012) AKT-aro and HER2-aro, models for de novo resistance to aromatase inhibitors; molecular characterization and inhibitor response studies. Breast Cancer Res Treat 134:671-81
Wong, Cynthie; Chen, Shiuan (2012) The development, application and limitations of breast cancer cell lines to study tamoxifen and aromatase inhibitor resistance. J Steroid Biochem Mol Biol 131:83-92
Wang, Yuanzhong; Zhou, Dujin; Phung, Sheryl et al. (2011) SGK3 is an estrogen-inducible kinase promoting estrogen-mediated survival of breast cancer cells. Mol Endocrinol 25:72-82
Su, Bin; Wong, Cynthie; Hong, Yanyan et al. (2011) Growth factor signaling enhances aromatase activity of breast cancer cells via post-transcriptional mechanisms. J Steroid Biochem Mol Biol 123:101-8

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