Studies on Tumor-suppressor Genes by Monochromosome Transfer

Abstract

The existence of tumor-suppressor genes has been primarily suggested by three lines of evidences : 1) Various transformed phenotypes are often suppressed in hybrids between normal and tumorigenic cells, and re-expression of the phenotypes in the hybrids is associated with loss of specific chromosomes. ; 2) non-random chromosome deletions in a variety of tumors ; 3) loss of heterozygosity in specific chromosomal regions in a variety of tumors. Results from transfer of candidate normal human chromosomes that might carry tumor-suppressor genes into various tumor cell lines, strongly support an idea that multiple tumor-suppressor genes are involved in a carcinogenic process of a given tumor. Three types of suppression were observed ; a) Induction of cellular senescence, b) Suppression of both the in vitro transformed properties and tumorigenicity, c) Suppression of the tumorigenicity. These findings further suggest the existence of functionally distinct tumor-suppressor genes. The loss of a suppressive function can be either genetic or epigenetic.