SUPPRESSION OF VARIOUS HUMAN TUMOR-CELL LINES BY A DOMINANT-NEGATIVE H-RAS MUTANT

A dominant negative H-ras mutant, N116Y, was transfected into a variet y of human tumor cell lines. N116Y extremely inhibited the proliferati on of A431 (vulva), PC3 (prostate), T24 (bladder), MCF7 (breast), NKPS and TMK1 (stomach) cancer cell lines. A431 and PC3 cells were particu larly susceptible to N116Y. In order to examine the effects of N116Y o n the neoplastic phenotypes, we transfected a less efficient N116Y exp ression vector into A431 cells. Almost all clones survived after G418 selection. However, they did not retain the N116Y gene and only one cl one faintly expressed N116Y. this N116Y-expressing clone had not tumor igenicity in vivo, and revealed deformed morphology and DNA fragmentat ion, suggesting that N116Y might have induced apoptotic cell death. Th us, N116Y may be applicable for gene therapy of a wide spectrum of hum an tumors.