PROTEIN-TYROSINE KINASE EXPRESSION DURING THE ESTROUS-CYCLE AND CARCINOGENESIS OF THE MAMMARY-GLAND

The susceptibility of the mammary epithelium to neoplastic transformat ion is linked to the exposure to estrogen during the estrous cycle. Th e effects of the estrous cycle on the mouse mammary gland have been in vestigated by analyzing H-3-thymidine incorporation, milk protein gene expression and DNA fragmentation. We found that the mammary epitheliu m undergoes limited proliferation, differentiation and apoptosis in a cycle-dependent manner. The estrous-responsive regulators of the mamma ry epithelium are unknown; however, considering the integral role of p rotein tyrosine kinases (PTKs) in the control of normal and malignant development, members of this family of enzymes are likely candidates f or such regulatory molecules. Using a RT-PCR-based cloning strategy, w e have undertaken a survey of PTKs expressed in the mammary gland at d efined stages of development, with special emphasis on the estrous cyc le. We identified 21 known and 4 novel PTKs. Their expression was anal yzed throughout mammary gland development and in mammary neoplasias us ing a transgenic mouse model for invasive and non-invasive carcinogene sis. Most of the identified PTKs showed highest expression during the estrous cycle and were down regulated during pregnancy and lactation. Deregulated expression was rarely observed in the non-invasive mammary tumors. In contrast, 10 of 19 PTKs expressed during the estrous cycle were also over-expressed in the invasive carcinomas, mostly involving members of the receptor family of PTKs. (C) 1995 Wiley-Liss, Inc.