Tumor Suppressor Genes in Prostate Cancer

Abstract

The concept of tumor suppressor genes (TSGs) was originally proposed on the basis of cell-fusion studies between neoplastic and nonneoplastic cultured cells (106, 133). These studies suggested the existence of chromosomal genetic elements in nonneoplastic cells that could suppress the malignant phenotype of fusion partners. Comings proposed that the process of neoplastic transformation involved the loss or inactivation of such suppressor elements, which in diploid organisms meant the alteration of both alleles of a given TSG locus (47). TSGs were thus viewed in counterpoise to the dominant oncogenes, for which proneoplastic activity was achieved via gain-of-function alterations (e.g., missense mutation, amplification, or overexpression) independent of the status of other alleles or loci (15). Both types of cancer genes have been integrated into general models of multistep carcinogenesis in which activated dominant oncogenes and inactivated TSGs contribute in a sequential or additive fashion to the process of cancer formation (68). Some workers have classified subgroups of TSGs that suppress only one aspect of the neoplastic phenotype, for example, “metastasis suppressors,” such as nm23-H1, or “invasion suppressors,” such as E-cadherin, but their genetic mechanism of loss or inactivation is analogous to that of all TSGs, and they are not otherwise distinguished here.