Increased expression and activity of repair genes TDP1 and XPF in non-small cell lung cancer.
Resistance to camptothecin (CPT), a topoisomerase I (Top1) inhibitor, is frequently encountered in non-small cell lung cancer (NSCLC) and CPT resistance is linked with TDP1, an enzyme capable of cleaving the covalent linkage between stabilized Top1 with DNA. The aim of this study is to evaluate the in vivo expression level of TDP1, as well as parallel repair pathway components XPF and MUS81, in primary NSCLC. We collected 30 un-matched and 4 NSCLC samples matched with normal lung tissue and 8 samples of non-neoplastic lung tissue from patients with and without lung cancer, and determined the protein expression of these three genes using Western blot and TDP1 activity by a specific enzymatic assay. Both TDP1 and XPF were overexpressed in over 50% of NSCLC tissues, with wide ranges of expression levels. MUS81 did not exhibit alteration in expression. Overexpression of TDP1 and XPF is common in NSCLC, and is therefore of interest as a possible contributor to drug resistance in NSCLC.
Liu
Chunyan
C
Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Division, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
Zhou
Shaoyu
S
Begum
Shahnaz
S
Sidransky
David
D
Westra
William H
WH
Brock
Malcolm
M
Califano
Joseph A
JA
D002166:Camptothecin; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D004720:Endonucleases; C498772:MUS81 protein, human; D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; D002166:Camptothecin