INTERACTION OF HORMONES AND KGF IN MAMMARY GROWTH

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DESCRIPTION (Adapted from the applicant's abstract): The long term objective of these studies is to understand the composition and organization of hormone/growth factor networks that mediate stromal/epithelial cell interactions in the mammary gland. The investigator proposes that mammogenic hormones and keratinocyte growth factor (KGF) constitute a stromal/epithelial paracrine pathway important for regulation of normal mammary epithelial cell growth that becomes magnified during preneoplastic and neoplastic growth in hormone dependent cancers. The hypothesis is that mammogenic hormones modulate epithelial cell sensitivity to KGF, and that KGF plays a significant role in altered growth regulation occurring in hormone sensitive preneoplasias and hormone dependent tumors. To address this, the investigator proposes : 1. To examine if the sensitivity of normal mammary epithelium to the growth promoting effects of KGF is altered by mammogenic hormones in cells cultured in a serum free, collagen gel culture system in which the cells grow and undergo morphogenesis within a three dimensional matrix. 2. To examine if the growth of preneoplasias and hormone sensitive tumors is stimulated by KGF, and to examine whether the sensitivity of this process is modulated by mammogenic hormones. 3. test whether mammogenic hormones modulate the expression of KGF receptor in the above tissues by RNAse protection analysis, and by receptor cross linking to iodinated growth factor in cultured cells, and 4. examine if preneoplasias and hormone dependent tumors express KGF, and if KGF regulates epithelial cell proliferation in these tissues in explant culture or in vivo.