The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents

DNA damage caused by alkylating agents results in a G2 checkpoint arrest. D NA mismatch repair (MMR) deficient cells are resistant to killing by alkyla ting agents and are unable to arrest the cell cycle in G2 phase after alkyl ation damage. We investigated the response of two MMR-deficient prostate ca ncer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies r eveal that DU145 cancer cells are more sensitive to killing by MNNG than LN CaP, Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensi tivity of MMR-deficient prostate cancer cells to alkylating agents, (C) 200 0 Academic Press.