DNA polymerase kappa, implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer

DNA polymerase kappa (Pol kappa) is a newly identified low-fidelity polymerase implicated in spontaneous and DNA damage-induced mutagenesis. As an initial study to investigate its possible involvement in tumorigenesis, we compared the expression level of Pol kappa in tumors and adjacent nontumorous...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-07, Vol.61 (14), p.5366-5369
Main Authors: O-Wang, J, Kawamura, K, Tada, Y, Ohmori, H, Kimura, H, Sakiyama, S, Tagawa, M
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Blotting, Northern
Blotting, Southern
Carcinoma, Non-Small-Cell Lung - enzymology
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
DNA Damage
DNA, Neoplasm - genetics
DNA-Directed DNA Polymerase
Female
Gene Amplification
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms - enzymology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Middle Aged
Mutagenesis
Proteins - genetics
RNA, Neoplasm - genetics
RNA, Neoplasm - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DNA polymerase kappa (Pol kappa) is a newly identified low-fidelity polymerase implicated in spontaneous and DNA damage-induced mutagenesis. As an initial study to investigate its possible involvement in tumorigenesis, we compared the expression level of Pol kappa in tumors and adjacent nontumorous tissues by Northern blot, semiquantitative RT-PCR, and Western blot analyses. In this study, paired tumor and normal specimens from 29 patients with stages I to IIIb non-small cell lung cancer (NSCLC), including 13 adenocarcinomas, 15 squamous cell cancers, and 1 adenosquamous carcinoma, were analyzed, among which different levels of tumor-associated Pol kappa overexpression were observed in 21 of 29 matched specimens. In addition, five matched specimens exhibited elevated Pol kappa expression in both tumor and control tissues, whereas only one nontumorous tissue expressed a higher level of Pol kappa than its tumor counterpart. The preferential up-regulation of Pol kappa expression in tumors was highly significant (P < 0.001). There was no apparent correlation of Pol kappa expression levels with tumor histology, grade, and stage or with smoking history. Southern blot analysis did not show amplification of the Pol kappa gene, indicating that the elevated Pol kappa expression is likely attributable to dysregulated transcription. Our data suggest that Pol kappa may contribute to lung tumor development by accelerating the accumulation of mutations.
ISSN:0008-5472