Abstract

This proposal outlines a time-course analysis of the gene induction pattern in the mammary gland in response to estrogen signaling and to PyV infection, and the definition of its cell-specificity and developmental stage-specificity.
Aim 1 will study the expression of fos and jun in the mammary gland in response to estrogen treatment, define its cell specificity, characterize the mitogenic response, and examine any delayed paracrine fos and jun and mitogenic responses in neighboring cells.
Aim 2 will compare the cell specific pattern of gene induction mediated by estrogen at different stages of mammary gland development.
Aim 3 will define the pattern of PyV infection in the mammary gland with regard to the level and cell specificity of viral gene expression, genome replication, induction of cellular genes, and induction of hyperplastic, dysplastic, and neoplastic lesions; and compare this pattern in mice infected at different stages of mammary gland development.
Aim 4 will define the stages of tumor development that are sensitive to estrogen.
Aim 5 will compare the properties of estrogen-dependent and estrogen-independent tumors with regard to the expression of a set of viral and cellular genes analyzed also in earlier Aims.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA058763-06
Application #
6171940
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Wong, May
Project Start
1993-01-01
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2002-08-31
Support Year
6
Fiscal Year
2000
Total Cost
$190,665
Indirect Cost

  Institution

Name
Michigan State University
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Fluck, Michele M; Schaffhausen, Brian S (2009) Lessons in signaling and tumorigenesis from polyomavirus middle T antigen. Microbiol Mol Biol Rev 73:542-63, Table of Contents
Wirth, J J; Chen, L; Fluck, M M (2000) Systemic polyomavirus genome increase and dissemination of capsid-defective genomes in mammary gland tumor-bearing mice. J Virol 74:6975-83
Wirth, J J; Martin, L G; Fluck, M M (1997) Oncogenesis of mammary glands, skin, and bones by polyomavirus correlates with viral persistence and prolonged genome replication potential. J Virol 71:1072-8
Fluck, M M; Haslam, S Z (1996) Mammary tumors induced by polyomavirus. Breast Cancer Res Treat 39:45-56
Rondinelli, R H; Haslam, S Z; Fluck, M M (1995) The role of ovarian hormones, age and mammary gland development in polyomavirus mammary tumorigenesis. Oncogene 11:1817-27