Heterogeneity in Expression of DNA Polymerase β and DNA Repair Activity in Human Tumor Cell Lines
The 39-kDa DNA polymerase β (polβ) is an essential enzyme in short-patch base excision repair pathway. A wild-type and a truncated forms of polβ proteins are expressed in primary colorectal and breast adenocarcinomas and in a primary culture of renal cell carcinoma. To test whether polβ has a contributory role in tumorigenicity of human tumor cell lines, we have undertaken a study to determine expression of polβ in colon, breast, and prostate tumor cell lines. Unlike primary colon tumor cells, three types of polβ mRNA have been identified in HCT 116, LoVo, and DLD1, colon tumor cell lines. A 111-bp-deleted polβ transcript was expressed in MCF7, a breast tumor cell line, but not in primary breast tumor cells. An expression of a smaller polβ transcript has been revealed in DU145, a prostate tumor cell line, whereas, a single base (T) deletion in mRNA at codon 191 was found in prostate cancer tissue. Interestingly, a wild-type polβ transcript was also expressed in all tumor cell lines similar to primary tumor cells. Furthermore, the cell extract of LoVo exhibited highest gap-filling synthesis function of polβ when the extract of DU145 showed lowest activity. MNNG, a DNA alkylating agent, enhanced the gap-filling synthesis activity in extracts of LoVo cell line. Furthermore, the cellular viability of LoVo and HCT116 cells is sensitive to MNNG when DU145 cells are resistant. These results demonstrate heterogeneity in polβ mRNA expression, which may be a risk factor related to tumorigenic activities of tumor cell lines.
No Supplementary Data
No Article Media
Document Type: Research Article
Affiliations: Department of Cancer Biology/NB40, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Publication date: March 1, 2002
More about this publication?
- Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.