Cloning of Tumor Suppressor Genes in Breast Cancer

摘要

Breast cancer arises through the accumulation of genetic alterations that affect two classes of genes, ongogenes and tumor suppressor genes. These genes must be identified for several reasons. Characterization of the genes that drive carcinogenesis will facilitate a better understanding of cancer development. As part of this big picture, we have studied tumor suppressor genes involved in breast cancer. A tumor suppressor candidate, DBC2 was analyzed. DBC2 is composed of a RAS domain, protein-protein interacting domains, and DNA binding domain. DBC2 expression is extinguished by hypermethylation in more than half of breast tumors we tested. When DBC2 expression was induced in tumor Cells, the cell growth was expressed. Additionally, mutants we discovered in breast cancer specimens were found to lack the tumor suppressor function. We are studying DBC2's physiological roles by expression microarray analysis, protein- protein interaction studies, and functional analysis. We have identified several genes upregulated by DBC2 and potential candidates for interaction. We have also established techniques to control DBC2 expression, both induction and suppression, which will facilitate further analysis of DBC2.