Characterizing the Role of 1p36 Deletion in Breast Cancer and Identifying Candidate Tumor Suppressors
Annual rept. 1 Apr 2006-31 Mar 2009
CALIFORNIA UNIV SAN FRANCISCO
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Over 60 of human breast tumors display a deletion of one copy of the 1p36 region of the short arm of chromosome 1. Patients whose tumors carry this deletion show a three-fold increase in mortality, suggesting a biological role for this deletion in tumor development, and suggesting the presence of one or more tumor suppressors in this region. Purpose Characterization of the unique biology of tumors with 1p36 deletion, and identification of the tumor suppressors in the region may inform therapeutic strategies, and present unique therapeutic targets for this subset of breast cancer cases with relatively poor survival. Scope The goals of this research project are to 1 develop a mouse model for 1p36 deletion in breast cancer by generating mice harboring loxP sequences flanking the deletion region, and crossing to tissue-specific Cre expressing mice, 2 perform in-vivo insertional mutagenesis in breast tumors using the two-component Sleeping Beauty transposon system mutagenic transposons mobilized by a trans-acting transposase to tag tumor suppressors and oncogenes during tumor development and 3 to combine these two systems to identify tumor suppressors in the 1p36 region. Technical setbacks and the observation by another group that deletion of at least part of the 1p36 region systemically does not lead to breast tumors in mice have led us to focus primarily on the Sleeping Beauty system for the last two years. We have opted for an in vitro approach in which we use lentiviral constructs to activate transposons in mammary epithelial cells, which we then transplant into recipient mice.
- Anatomy and Physiology
- Medicine and Medical Research