Poly(ADP-ribose) polymerase-1 gene in human tumor cell lines: Its expression and structural alteration

Poly(ADP-ribose) polymerase-1 (Parp-1) is involved in DNA repair and cell-death induction after DNA damage. Parp-1-/- mice show higher susceptibility to the carcinogenic effects of nitrosamine and azoxymethane. To elucidate the role of alterations of the PARP-1 gene in human carcinogenesis, we examined the expression level of PARP-1 gene in various human tumor cell lines. The presence of gross rearrangement of PARP-1 gene in these cell lines was also examined by Southern blot hybridization analysis. The expression levels of PARP-1 gene in several cell lines, including T-cell leukemia cell lines (Molt-4 and CCRF-CEM), colon cancer cell line (WiDr), and gastric cancer cell lines (KatoIII, OKAJIMA, and MKN45) was substantially lower than in other cancer cell lines. Among the 85 analyzed cell lines, structural alteration of PARP-1 gene was detected in a gastric cancer cell line, MKN28. A low level of PARP-1 expression in human cancer could potentially influence cancer cell growth, differentiation and cancer development by affecting genomic instability, as well as the response of tumors to chemo- and radiotherapy. (Contributed by Takashi SUGIMURA, M.J.A., Feb. 12, 2004)