Abstract

The long-term objective of this project is to generate information useful for controlling aromatase action in breast cancer patients. Using immunocytochemistry and reverse transcriptation-polymerase chain reaction (RT-PCR), aromatase was found to be expressed in approximately 40% of the breast tumors examined. A nude mouse model with mice bearing aromatase-expressing tumors has been established. The clinical significance of in situ aromatization in breast cancer cells will be studied using such an in vivo model. The organization of the human aromatase gene will be investigated. The regulatory mechanism of aromatase expression in different aromatase expressing cells by hormones, and other reagents will also be investigated. The promoters and regulatory elements involved in regulating aromatase expression in breast cancer cells will be identified and characterized. In addition, site-directed mutagenesis and active site-labeling experiments will be applied to generate structural information at the active site region of aromatase. The information obtained can be used in the design of more effective treatment of breast cancer by aromatase inhibitors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044735-10
Application #
2856276
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Mohla, Suresh
Project Start
1988-07-01
Project End
1999-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
10
Fiscal Year
1999
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; 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
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
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

Showing the most recent 10 out of 103 publications