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Heterogeneity in Expression of DNA Polymerase β and DNA Repair Activity in Human Tumor Cell Lines

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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.
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Keywords: DNA pol Human tumor cell lines; mRNA Protein Gap-filling synthesis DNA binding MNNG

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

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