Abstract

The long-term objective of this grant application is to understand the cellular and molecular basis for mammary gland preneoplastic transformation. The essential biological characteristics of mammary preneoplasias have been adequately described, however the cell and molecular correlates of these properties are unknown. The recent description of appropriate methods to grow and chemically transform mammary epithelial cells in vitro and the explosive documentation of the existence and properties of proto- oncogenes provide new avenues to understand long sought after goals. In this application, the aims are to examine specific cellular and molecular properties which may be the basis for the observed properties of mammary preneoplasias. Specifically, mammary epithelial cells will be transformed in vitro in a collagen-extracellular matrix gel and the cells assayed for transformation properties in vivo. The treated cells will be examined for alterations in growth factor dependence, proto- oncogene expression (those proto-oncogenes that are homologues of hormone receptors), altered keratin expression as well as morphological types of preneoplasias.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA047112-01
Application #
3190598
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Medina, D (2000) The preneoplastic phenotype in murine mammary tumorigenesis. J Mammary Gland Biol Neoplasia 5:393-407
Stickeler, E; Kittrell, F; Medina, D et al. (1999) Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesis. Oncogene 18:3574-82
Bonnette, S G; Kittrell, F S; Stephens, L C et al. (1999) Interactions of apoptosis, proliferation and host age in the regression of the mouse mammary preneoplasia, TM3, carrying an unusual mutation in p53. Carcinogenesis 20:1715-20
Raught, B; Gingras, A C; James, A et al. (1996) Expression of a translationally regulated, dominant-negative CCAAT/enhancer-binding protein beta isoform and up-regulation of the eukaryotic translation initiation factor 2alpha are correlated with neoplastic transformation of mammary epithelial cells. Cancer Res 56:4382-6
Medina, D (1996) Preneoplasia in mammary tumorigenesis. Cancer Treat Res 83:37-69
Jerry, D J; Medina, D; Butel, J S (1994) p53 mutations in COMMA-D cells. In Vitro Cell Dev Biol Anim 30A:87-9
Jerry, D J; Ozbun, M A; Kittrell, F S et al. (1993) Mutations in p53 are frequent in the preneoplastic stage of mouse mammary tumor development. Cancer Res 53:3374-81
Medina, D; Kittrell, F S (1993) Immortalization phenotype dissociated from the preneoplastic phenotype in mouse mammary epithelial outgrowths in vivo. Carcinogenesis 14:25-8
Ozbun, M A; Medina, D; Butel, J S (1993) p53 mutations in mouse mammary epithelial cells: instability in culture and discordant selection of mutations in vitro versus in vivo. Cell Growth Differ 4:811-9
Zhang, L; Medina, D (1993) Gene expression screening for specific genes associated with mouse mammary tumor development. Mol Carcinog 8:123-6

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