Analysis of Tumor Suppressor Gene Loss in Mouse Mammary Models of Mammary Neoplasia

摘要

The original sabbatical proposal was modified to two separate aims, both designed to acquire knowledge of genetics to be applied to mammary carcinoma. These studies were carried out at Stanford University in the laboratories of Stuart Kim, David Botstein and Pat Brown. First, in the Kim lab, a genetic screen was performed in C.elegans in a sensitized background (using worms mutant for Gap) to identify worms that missorted Let-23, the worm EGF receptor, in polarized vulva precursor cells. By complementation testing and STS mapping, a locus has been identified on chromosome 4 that results in missorting of Let-23 from the basolateral to apical surface. Second, microarray technology in the Botstein and Brown labs was utilized to identify sets of genes that are induced by antioxidants in mammary and colorectal carcinoma cells that culminate in p53-independent, p2l-dependent apoptosis. Candidate genes have been identified and are being characterized. In addition, the latter experience enabled me to develop a microarray core lab at Vanderbilt University.