Extraneuronal monoamine transporter expression in human tumor cell lines
10.3321/j.issn:1000-467X.1999.05.005
- VernacularTitle:神经元外单胺转运蛋白在人肿瘤细胞系的表达
- Author:
Zhong-Ping CHEN
1
;
GerardMohr
;
LawrenceC.Panasci
Author Information
1. 中山医科大学附属肿瘤医院
- Keywords:
Extraneuronal monoamine transporter;
2-Chloroethy1-3-sarcosinamide-1-nitrosourea;
Human tumor cell line
- From:Chinese Journal of Cancer
1999;18(5):504-508
- CountryChina
- Language:Chinese
-
Abstract:
Objective:We previously have found that 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU),a new chloroethylnitrosourea analogue, which is in phase I clinical trials,is a selective cytotoxin that enters cells via the extraneuronal transporter for monoamine transmitters (EMT). In the present study,we determined EMT expression in 23 human tumor cell lines in order to verify if EMT expression correlate to SarCNU cytotoxicity. Methods:Reverse-transcription polymerase chain reaction (RT-PCR) was used for determination of EMT expression in tumor cell lines.We also measured expressions of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) and excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2) by Western blot analysis. The results were correlated to SarCNU cytotoxicity which was determined by the sulforhodamine B (SRB) colorimetric anticancer-drug screening assay. Results:Almost all of the cell lines tested were positive for EMT expression,while five cell lines (MGR-1,MGR-2,T98-G,SKI-1,and GBM) were very low expressors. Although there was no significant linear correlation between SarCNU cytotoxicity and EMT expression,multiple regression analysis demonstrated a significant correlation between SarCNU cytotoxicity and EMT plus MGMT and ERCC-2 expression. Conclusions:This study suggests that both EMT and DNA repair factors, specifically,MGMT and ERCC2 are important determinants of SarCNU activity against human tumor cell lines.SarCNU should prove to be a more useful alternative chemotherapeutic agent for treatment of human tumors,since the majority of human tumor cell lines were EMT positive.
