PTEN, a Tumor Suppressor Gene for Prostate Cancer.

Inactivations of tumor suppressor genes are the most common genetic alterations in human cancers. The PTEN gene is a tumor suppressor gene recently cloned from human chromosome 10q23.3 that encodes a lipid phosphatase which influences a variety of cellular processes that impact on the neoplastic phenotype. The goal of this proposal is to characterize the role of the PTEN tumor suppressor gene in prostate cancer using the TRAMP mouse model, a well characterized transgenic mouse model of prostate cancer. Our research has shown that the region on mouse chromosome 19 homologous to human chromosome 10q23 is altered in a substantial fraction of TRAMP mouse prostate cancers as detected by analysis of loss of heterozygosity. We have not found a corresponding number of inactivating lesions of the retained PTEN allele, similar to the situation in clinically localized human prostate cancer as well as other human cancers such as breast cancer. We are now in a position to resolve this paradoxical observation by determining whether hemizygous loss of PTEN in itself promotes prostate tumorigenesis or whether there may be second tumor suppressor gene tightly linked to PTEN by analysis of tumor progression in PTEN heterozygote knockouts crossed with TRAMP mice