[Expression of extraneuronal monoamine transporter gene and DNA repair gene vis-à-vis with antitumor efficacy of SarCNU in human tumor xenografts].
OBJECTIVE
To clarify if there are any correlations between extraneuronal monoamine transmitters (EMT), DNA repair gene expressions and SarCNU antitumor efficacy.


METHODS
EMT, DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) and excision repair cross-complementing rodent repair deficiency gene (ERCC1-6) expressions in 9 human xenograft tumor models were determined by RT-PCR. The results were compared with the antitumor effects of SarCNU on these tumor xenografts.


RESULTS
Multiple regression analysis revealed significant correlations of SarCNU antitumor activity with different combinations of gene expression. The most significant correlation was observed with all of the 4 genes expressed.


CONCLUSIONS
The results suggest that expression of both EMT and DNA repair genes, specifically, MGMT, ERCC2 and ERCC4, are important determinants of SarCNU activity against human tumors. While DNA repair decreases SarCNU's activity by repairing damaged DNA, EMT appears to enhance its antitumor efficacy.
Chen
Z
Z
Cancer Institute, Tumor Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510060, China.
Panasci
L C
LC
Carter
C A
CA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002330:Carmustine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D027701:Organic Cation Transport Proteins; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051759:Xeroderma Pigmentosum Group D Protein; D000099254:Organic Cation Transporter 3
D000970:Antineoplastic Agents; D002330:Carmustine; D002352:Carrier Proteins; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D019853:O(6)-Methylguanine-DNA Methyltransferase; D027701:Organic Cation Transport Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein; D000099254:Organic Cation Transporter 3; C095888:xeroderma pigmentosum group F protein; C044565:2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide; C497292:ERCC2 protein, human; C497293:Ercc2 protein, mouse