title: The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.
abstract: DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. 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 sensitivity of MMR-deficient prostate cancer cells to alkylating agents.
authors.affiliation: Department of Life Sciences and Chemistry, Roskilde University, Denmark. ljr@virgil.ruc.dk
authors.forename: L J
authors.initials: LJ
authors.lastname: Rasmussen
authors.forename: M
authors.initials: M
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Lützen
authors.forename: H C
authors.initials: HC
authors.lastname: Bisgaard
authors.forename: K K
authors.initials: KK
authors.lastname: Singh
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D020137:Base Pair Mismatch; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D006801:Humans; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000477:Alkylating Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D008769:Methylnitronitrosoguanidine