DNA polymerase beta expression differences in selected human tumors and cell lines.
A long-standing question in cancer biology has been the extent to which DNA repair may be altered during the process of carcinogenesis. We have shown recently that DNA polymerase beta (beta-pol) provides a rate-determining function during in vitro repair of abasic sites by one of the mammalian DNA base excision repair pathways. Therefore, altered expression of beta-pol during carcinogenesis could alter base excision repair and, consequently, be critical to the integrity of the mammalian genome. We examined the expression of beta-pol in several cell lines and human adenocarcinomas using a quantitative immunoblotting method. In cell lines from normal breast or colon, the level of beta-pol was approximately 1 ng/mg cell extract, whereas in all of the breast and colon adenocarcinoma cell lines tested, a higher level of beta-pol was observed. In tissue samples, colon adenocarcinomas had a higher level of beta-pol than adjacent normal mucosa. Breast adenocarcinomas exhibited a wide range of beta-pol expression: one tumor had a much higher level of beta-pol (286 ng/mg cell extract) than adjacent normal breast tissue, whereas another tumor had the same level of beta-pol as adjacent normal tissue. Differences in beta-pol expression level, from normal to elevated, were also observed with prostate adenocarcinomas. All kidney adenocarcinomas tested had a slightly lower beta-pol level than adjacent normal tissue. This study reveals that the base excision repair enzyme DNA polymerase beta is up-regulated in some types of adenocarcinomas and cell lines, but not in others.
Srivastava
D K
DK
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Department of Functional Genetics, GlaxoWellcome Inc., Five Moore Drive, Research Triangle Park, NC 27709, USA.
Husain
I
I
Arteaga
C L
CL
Wilson
S H
SH
D000230:Adenocarcinoma / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology; D016466:CHO Cells; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology; D006224:Cricetinae; D019951:DNA Polymerase beta / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D005260:Female; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D019951:DNA Polymerase beta