Mammary carcinogenesis is a multistep process that requires the concerted action of multiple genes. These genes mediate several different morphogenetic transformation pathways characterized by partially- transformed protoneoplastic lesions. The long-term goal of the proposed research is to define the role of protooncogenes in this system. Our strategy is to (i) isolate and characterize new mammary protooncogenes identified by mouse mammary tumor virus (MMTV) insertion mutation, (ii) analyze mammary protooncogenes in rodent and human protoneoplasias, tumors, and cell culture systems, and (iii) reconstruct postulated transformation pathways using our transgenic mammary gland system. In the initial grant period, we propose to use our unique combination of molecular, biological, and clinical resources to (i) characterize mammary protooncogene expression vectors in transgenic mammary glands constructed in the MMTV-free WLC-0 mouse strain, (ii) isolate and characterize new protooncogenes activated by MMTV provirus insertion using mammary protoneoplasias and tumors from the WXG-2 mouse strain, and (iii) isolate and characterize human homologs of the new mammary protooncogenes identified in the mouse system and determine if these genes are also mutated during mammary carcinogenesis in humans.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054284-04
Application #
2095797
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Davis
Department
Pathology
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Cardiff, R D (1996) The biology of mammary transgenes: five rules. J Mammary Gland Biol Neoplasia 1:61-73
Cho, K; Ferrick, D A; Morris, D W (1995) Structure and biological activity of the subgenomic Mtv-6 endogenous provirus. Virology 206:395-402
Cardiff, R D; Muller, W J (1993) Transgenic mouse models of mammary tumorigenesis. Cancer Surv 16:97-113
Ferrick, D A; Cho, K; Gemmell-Hori, L et al. (1992) Genetic analysis of the effects of Mtv-2 on the T cell repertoire in the WXG-2 mouse strain. Int Immunol 4:805-10