Mammary Tumor Development: Stromal-Epithelial Interactions in Oncogenesis

摘要

The purpose of this grant was to study mammary oncogenesis in transgenic mice that expressed a virus-derived growth factor, Shope growth factor (SGF), which resembles epidermal growth factor (EGF). Shope growth factor (SGF). Lines of SGF transgenic mice expressed this cytokine using inducible (metallothionein, MT) and constitutive (RSV-LTR) promoters. We have found that expression of SGF in transgenic mice under the control of the RSV-LTR as a promoter led to profound changes in mammary gland histology, resulting in a pathologic and molecular phenotype that shows changes characteristic of%late pregnancy or lactation. These changes include mammary gland differentiation: acinar proliferation, distention of glands and ducts by proteinaceous material consistent in appearance with lactation products (i.e., milk production), and comparable changes in mammary ducts. Corresponding alterations have been seen in patterns of gene expression in these mammary glands: expression of lactation- associated genes such as whey acidic protein, t3-casein, and WDNMI, was increased in SGF-transgenic mice. Transgenic mice expressing SCF under the control of metallothionein promoter (MT-SGF) generally showed similar findings when MT promoter activity was induced by feeding with Zn2+. These findings have profound implications for understanding mammary oncogenesis and, in particular, its inhibition. 1% qiRi%rT Th%M%.