Abstract

The breast cancer susceptibility genes BRCA1 and BRCA2 account for the majority of familial breast cancers. The recent isolation of these genes by positional cloning has made it possible to investigate their functions as tumor suppressors and their impact on prognosis and treatment of breast cancer. We have generated evidence that both BRCA1 and 2 activate transcription of a specific subset of genes and have produced immunological reagents for the detection of the BRCA2 product. One major aim of this proposal is to elucidate mechanisms by which BRCA1 and 2 alter gene expression, including their interactions with other proteins. Studies in tissue culture will determine the subcellular localization of BRCA2 as well as the effects of increased or decreased expression of BRCA1 and 2 on biological responses to stress, radiation, therapeutic agents, and hormonal stimuli. Effort will also be made to establish cell lines from patients with familial breast cancer in order to characterize the effects of wild type gene expression in tumors in which BRCA1 or 2 functions have been inactivated. The knowledge gained should be useful in developing detection and treatment strategies specifically targeted to heritable breast cancers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA068425-05
Application #
6203333
Study Section
Project Start
1999-09-24
Project End
2001-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Navin, Nicholas E; Hicks, James (2010) Tracing the tumor lineage. Mol Oncol 4:267-83
Ueda, Yukiko; Su, Yingjun; Richmond, Ann (2007) CCAAT displacement protein regulates nuclear factor-kappa beta-mediated chemokine transcription in melanoma cells. Melanoma Res 17:91-103
Solit, David B; Scher, Howard I; Rosen, Neal (2003) Hsp90 as a therapeutic target in prostate cancer. Semin Oncol 30:709-16
Mu, David; Chen, Liyun; Zhang, Xiping et al. (2003) Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Cancer Cell 3:297-302
Solit, David B; Basso, Andrea D; Olshen, Adam B et al. (2003) Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Cancer Res 63:2139-44
Hamaguchi, Masaaki; Meth, Jennifer L; von Klitzing, Christine et al. (2002) DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci U S A 99:13647-52
Munster, Pamela N; Marchion, Douglas C; Basso, Andrea D et al. (2002) Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3'-kinase-AKT-dependent pathway. Cancer Res 62:3132-7
Subbaramaiah, Kotha; Norton, Larry; Gerald, William et al. (2002) Cyclooxygenase-2 is overexpressed in HER-2/neu-positive breast cancer: evidence for involvement of AP-1 and PEA3. J Biol Chem 277:18649-57
Basso, Andrea D; Solit, David B; Munster, Pamela N et al. (2002) Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2. Oncogene 21:1159-66
Solit, David B; Zheng, Fuzhong F; Drobnjak, Maria et al. (2002) 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 8:986-93

Showing the most recent 10 out of 51 publications