Initiating Events in Prostate Cancer: The Role of Somatic activation of Beta-Catenin
Abstract
Murine models of prostate cancer have been developed that rely on the somatic activation of beta-catenin. The approach employs Cre-loxP mediated targeted genetic recombination of the Catnb+lox(ex3) locus. Expression of Cre was targeted specifically to the prostate secretory epithelium using androgen responsive minimal probasin (PB) or prostate specific antigen (PSA) gene promoters. Lesions produced by PB-Cre were limited in comparison to the previously reported MMTV-Cre mice, while PSA-Cre caused highly inflamed and invasive lesions. In contrast to the MMTV-Cre, no squamous metaplasia was produced by the PB- or PSA-Cre. No lesions were detected with K14-Cre mice, that target expression of Cre to basal cells. These observations are likely to be related to the type of cells or stages of differentiation targeted by each promoter. The ontogeny of PINs and carcinomas are being traced, using simultaneous Cre dependent expression of lacZ. In a limited screen of clinical histology samples, stabilization of beta-catenin in PIN lesions was readily detected in some but not all PIN lesions. NKCCl was generally not extinguished in human PINs, as well as in murine prostate cancers caused by genetic alterations other than (beta-catenin (SV4O-T, or active AKT). Potential cross talk of the beta-catenin and Pl3kinase signaling pathways, and downstream gene targets in prostate cancer are under investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427939
Entities
People
- Gouying Zhang
- Khashayarsha Khazaie
- Mei L. Chen
- Mikael Pittet
Organizations
- Dana–Farber Cancer Institute