Identification of Tumor Suppressor Genes in Breast Cancer by Insertional; Mutagenesis and Functional Inactivation (96 Breast)

摘要

The development and progression of cancer result from multiple genetic changes accumulated in the cells. The identification of tumor suppressor genes inactivated and proto-oncogenes activated in mammary epithelial cells is essential to understand the genetic basis of breast cancer and is a prerequisite for development of strategies for prevention, diagnosis, and treatment. In breast cancer, loss of heterozygosity (LOR) was detected frequently on chromosome 17 and other chromosomes, suggesting unrecognized tumor suppressor genes. We are applying the novel retroviral-tagging strategy to identify the genes using chromosome 1 7-suppressed (independent of p53 and ERCAl) breast cancer cell lines. In contrast to the parental tumorigenic cell line CAL51, the suppressed sublines CAL/17-1, CAL/17-3 and CAL/17-5 display insulin-dependent growth in flasks, no growth in soft-agar culture and athymic nude mice. In this annual report, we present our results on selection for the anchorage-independent cell sublines induced by retroviral transduction of the chromosome 17-mediated suppressed cell lines CAL/ 17, in addition to successful selection for insulin- independent cell sublines. We are now in the process to conduct tumorigenicity tests in athymic nude mice and to clone genomic sequences flanking the integrated retroviral vectors.