Heterogeneity in expression of DNA polymerase beta and DNA repair activity in human tumor cell lines.

Abstract:

The 39-kDa DNA polymerase beta (pol beta) is an essential enzyme in short-patch base excision repair pathway. A wild-type and a truncated forms of pol beta proteins are expressed in primary colorectal and breast adenocarcinomas and in a primary culture of renal cell carcinoma. To test whether pol beta has a contributory role in tumorigenicity of human tumor cell lines, we have undertaken a study to determine expression of pol beta in colon, breast, and prostate tumor cell lines. Unlike primary colon tumor cells, three types of pol beta mRNA have been identified in HCT116, LoVo, and DLD1, colon tumor cell lines. A 111-bp-deleted pol beta transcript was expressed in MCF7, a breast tumor cell line, but not in primary breast tumor cells. An expression of a smaller pol beta 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 pol beta 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 pol beta 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 pol beta mRNA expression, which may be a risk factor related to tumorigenic activities of tumor cell lines.

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