Tissue Specific Chromosome Deletions: An In Vivo Genetic Screen for Tumor Suppressor Genes in the Mammary Glands.

摘要

Breast cancer is a genetic disease and it is important to define which genes are significant mutational targets in sporadic breast tumors so that treatments can be directed based on the knowledge of the genetic changes in the tumor. This project was focused on identifying tumor suppressor genes which are mutated in sporadic breast cancer using a novel genetic screen. This genetic screen involved applying chromosome engineering technology to delete specific chromosomal regions in mouse mammary epithelial cells in vivo, which should allow the induction of tumor suppressor mutations in these haploid regions. We have established that tissue specific expression of cre can efficiently recombine loxP sites even when they are several megabases apart. In order to achieve recombination in mammary epithelial cells we have been developing several cre lines. These include an MMTV-Cre line targeted to the Hprt locus as well as a line in which Cre has been knocked into the beta-casein locus. We have been evaluating the specificity of these lines using a reporter strain in which lacZ is activated following the expression of Cre. When a line with the desired tissue specificity is obtained, tissue specific induced chromosome deletions will be performed with relevant chromosomal regions. Substantial progress on this work was published (Methods 24: 81-94, 2001).