Initiating Events in Prostate Cancer: The Role of Somatic Activation of Beta-Catening
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. We were able to demonstrate that the target of transformation by beta-catenin in the prostate is the secretory epithelia. We have provided evidence for the benign nature of transformation by beta-catenin and the conversion of this benign phenotype to invasive cancer upon heterozygous loss of PTEN. Local inflammatory reactions were shown to be inherently associated with and contribute to the local tumor microenvironment, suggesting a crosstalk between tumor and host immune response that may be contributing to the success of the tumor. Future work will focus on the contribution of the PTEN mutation to tumor progression, the contribution of local inflammatory responses, and studies of downstream targets of beta-catenin in the prostate physiology and cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA441729
Entities
People
- Khashayarsha Khazaie
Organizations
- Dana–Farber Cancer Institute