Einfluss des Proto-Onkogens bcl-2 auf die Apoptose alveolaerer Brustepithelzellen und auf die experimentell induzierte Tumorigenese der Brust, des Darms und der Haut in transgenen Maeusen

Expression of bcl-2, a proto-oncogene causally involved in the development of follicular lymphoma in man, is also found in various tumours of epithelial origin including breast, colon and skin. Bcl-2 is a member of a family of homologous proteins controlling apoptotic cell death. In lymphoma Bcl-2 exerts its oncogenic action by its capability of suppressing apoptosis. However, its possible role in the development of epithelial tumours remains to be investigated. To adress this question experimentally, transgenic mice have been generated which overexpress Bcl-2 (a) in their mammary glands, (b) in their intestine, and (c) in suprabasal layers of the skin. While the effects of Bcl-2 expression on the development of experimentally induced tumors of the intestine and of the skin remained unclear, Bcl-2 accelerated the c-Myc-induced mammary tumor formation. Moreover, the high rate of apoptosis in the breast epithelium induced by c-Myc was significantly decreased by Bcl-2. In addition, Bcl-2 was capable of suppressing apoptosis of alveolar mammary epithelial cells induced by postlactational involution or a WAPp53 transgene, respectively. These findings suggest that, by analogy to lymphoma, Bcl-2 contributes to mammary tumorigenesis by suppressing apoptosis. (orig.)SIGLEAvailable from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman