Human breast and ovarian cancer together account for 162,000 new cases of cancer per year or essentially one third of all cancers occurring in women. In addition, they account for 55,000 deaths per year, or essentially one quarter of cancer related deaths in women. The HER-2/neu proto-oncogene is a putative growth factor receptor which is related to, but distinct from the epidermal growth factor receptor. Studies done in our laboratory have shown that this gene is amplified and/or overexpressed in ~30% of human breast and ovarian cancers. Moreover, this alteration is associated with a poor clinical outcome for patients in whose tumors it occurs. The objective of this proposal is to investigate the possible role this alteration plays in the pathogenesis of these diseases. Transfection studies will be done to convert human breast and ovarian cells from cells with a single copy and low levels of expression of the HER-2/neu gene to cells with an amplified/overexpressed gene mimicking the alteration found in human breast and ovarian cancer. The biologic effects of this alteration will be investigated, including effects on DNA synthesis, cell growth, cell invasiveness, and tumorigenicity in the nude mouse. In addition, antibodies to extracellular domains of this gene product will be used in vitro and in vivo studies of cells containing this alteration to determine if the antibodies change the biologic effects mediated by this alteration. These studies may lead to development of novel therapeutic approaches to these diseases based on this oncogene alteration.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA032737-17S1
Application #
6327587
Study Section
Project Start
1999-07-22
Project End
2002-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
17
Fiscal Year
2000
Total Cost
$181,487
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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