Abstract

Proto-oncogenes and tumor suppressor genes represent a cohort of cellular genes which are known to play central roles in the normal growth and proliferation of vertebrate cells. Increasing evidence indicates that alterations in these genes play a role in the induction and/or maintenance of many if not all human malignancies. The purpose of this program is to continue work ongoing over the past eight years to identify and characterize alterations in these genes in a variety of human malignancies. The program is designed to screen human tumor tissues using nucleic acid and antibody probes for genes Of interest to detect patterns of alterations in various groups of malignancies. As a result of this approach the program has been effective in identifying proto-oncogene alterations which may be important in the pathogenesis of human breast and ovarian cancers and has used this information as well as information generated by other laboratories to generate reagents to study the role these alterations play on the biology of the diseases in which they occur. We propose to use these studies to gain new insights into the diagnosis, prognosis and treatment of human malignancies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036827-10
Application #
3174410
Study Section
Pathology B Study Section (PTHB)
Project Start
1984-07-01
Project End
1997-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Wilson, C A; Ramos, L; Villasenor, M R et al. (1999) Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 21:236-40
Pietras, R J; Poen, J C; Gallardo, D et al. (1999) Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene. Cancer Res 59:1347-55
Pietras, R J; Pegram, M D; Finn, R S et al. (1998) Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 17:2235-49
Pegram, M D; Finn, R S; Arzoo, K et al. (1997) The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 15:537-47
Reese, D M; Slamon, D J (1997) HER-2/neu signal transduction in human breast and ovarian cancer. Stem Cells 15:1-8
Wilson, C A; Payton, M N; Elliott, G S et al. (1997) Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-delta11b. Oncogene 14:1-16
Pauletti, G; Godolphin, W; Press, M F et al. (1996) Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 13:63-72
Pisani, A L; Barbuto, D A; Chen, D et al. (1995) HER-2/neu, p53, and DNA analyses as prognosticators for survival in endometrial carcinoma. Obstet Gynecol 85:729-34
Silverstein, M J; Poller, D N; Waisman, J R et al. (1995) Prognostic classification of breast ductal carcinoma-in-situ. Lancet 345:1154-7
Pietras, R J; Arboleda, J; Reese, D M et al. (1995) HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 10:2435-46

Showing the most recent 10 out of 29 publications