Elevated expression of DNA polymerase beta gene in glioma cell lines with acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea.
We investigated the expression of DNA polymerase beta (beta-pol) and O6-methylguanine-DNA methyltransferase (MGMT) in human glioma cells with acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU) and in the parent cells. ACNU-resistant T430 (T430R) and A172 (A172R) glioma cell lines were established following repeated exposure to ACNU. The level of MGMT mRNA expression was elevated in T430R, but not in A172R. In contrast, the level of beta-pol mRNA expression and the level of beta-pol protein were elevated in A172R, compared with the parent cells. While the mechanism of MGMT repair has been considered to be important in the drug resistance of human brain tumors to ACNU, our present results demonstrate that beta-pol may also play an important role in the acquisition of tumor cell resistance to ACNU in human gliomas.
Gomi
A
A
Department of Surgical Neurology, Jichi Medical School, Tochigi, Japan. gomi@wt.net
Shinoda
S
S
Sakai
R
R
Hirai
H
H
Ozawa
K
K
Masuzawa
T
T
D000970:Antineoplastic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D004256:DNA Polymerase I / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma; D005910:Glioma; D006801:Humans; D015376:Nimustine / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D015376:Nimustine; D004256:DNA Polymerase I