Abstract

Based on their preliminary data that levels of RbAp46 expression decline during the progression of proliferative breast disease in the MCF10AT xenograft model and in malignant breast cancer cells, the investigators propose to: 1. Study the effects of constitutive expression on estrogen-stimulated progression using the MCF10AT xenograft model, and examine the levels of RbAp46 expression in human clinical samples using immunohistochemistry and/or RT-PCR. 2. Study the biological significance of the interaction between RbAp46 and the product of BRCA1 using in vivo and in vitro binding assays, as co-immunoprecipitation and GST capture assays, and RbAp46 and BRCA1 interaction and co-localization during the cell cycle and after exposure to DNA damage agents. 3. Study the molecular mechanisms by which RbAp46 inhibits cell growth and suppresses malignant transformation by examining the Ras pathway in MCF10At cells, and structure/ functional analyses to determine the domains of RbAp46 that are required for its growth inhibition and interaction with BRCA1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA084328-03
Application #
6514300
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Ault, Grace S
Project Start
2000-07-01
Project End
2003-05-01
Budget Start
2002-07-01
Budget End
2003-05-01
Support Year
3
Fiscal Year
2002
Total Cost
$234,900
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Lee, Lisa M J; Cao, Jiang; Deng, Hao et al. (2008) ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas. Anticancer Res 28:479-83
Zhang, Teng-Fei; Yu, Shui-Qing; Wang, Zhao-Yi (2007) RbAp46 inhibits estrogen-stimulated progression of neoplastigenic breast epithelial cells. Anticancer Res 27:3205-9
Li, Guan-Cheng; Wang, Zhao-Yi (2006) Constitutive expression of RbAp46 induces epithelial-mesenchymal transition in mammary epithelial cells. Anticancer Res 26:3555-60
Li, Guan-Cheng; Wang, Zhao-Yi (2006) Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression. Anticancer Res 26:4511-8
Chang, Yunchao; Berenson, James R; Wang, Zhaoyi et al. (2006) Dominant negative pleiotrophin induces tetraploidy and aneuploidy in U87MG human glioblastoma cells. Biochem Biophys Res Commun 351:336-9
Wang, Zhaoyi; Zhang, Xintian; Shen, Peng et al. (2006) A variant of estrogen receptor-{alpha}, hER-{alpha}36: transduction of estrogen- and antiestrogen-dependent membrane-initiated mitogenic signaling. Proc Natl Acad Sci U S A 103:9063-8
Wang, Zhaoyi; Zhang, Xintian; Shen, Peng et al. (2005) Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66. Biochem Biophys Res Commun 336:1023-7
Zhang, Xintian; Shen, Peng; Coleman, Megan et al. (2005) Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17beta-estradiol-stimulated mammary tumorigenesis. Anticancer Res 25:369-75
Zhang, Teng-Fei; Yu, Shui-Qing; Loggie, Brian W et al. (2003) Inducible expression of RbAp46 activates c-Jun NH2-terminal kinase-dependent apoptosis and suppresses progressive growth of tumor xenografts in nude mice. Anticancer Res 23:4621-7
Zhang, Teng-Fei; Yu, Shui-Qing; Guan, Li-Shuang et al. (2003) Inhibition of breast cancer cell growth by the Wilms' tumor suppressor WT1 is associated with a destabilization of beta-catenin. Anticancer Res 23:3575-84

Showing the most recent 10 out of 13 publications