ONCOGENESIS BY POLYOMAVIRUS--A MODEL FOR BREAST CANCER

Michigan State University, East Lansing MI

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Abstract

DESCRIPTION (Adapted from the applicant's 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.