title: mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity to cisplatin, carboplatin and gemcitabine in human lung cancer cell lines.
abstract: OBJECTIVE
  Expression of genes involved in DNA repair and/or DNA synthesis, including ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) has been reported to be associated with chemosensitivity to platinum agents and gemcitabine. The aim of this study was to test whether similar associations would be seen between mRNA expression for the RRM1, ERCC1 and ERCC2 genes and in vitro chemosensitivity in lung cancer.
  
  
  METHODS
  Using a panel of 20 lung cancer cell lines, including 15 NSCLC and 5 small cell lung cancers (SCLC), the mRNA expression levels for the RRM1, ERCC1 and ERCC2 genes were examined by quantitative real-time reverse transcription PCR. The in vitro cytotoxicity of cisplatin, carboplatin and gemcitabine was assessed using a tetrazolium-based colorimetric assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay).
  
  
  RESULTS
  Significantly, higher RRM1 mRNA expression was found in SCLC compared with NSCLC. However, there were no correlations between mRNA expression of the ERCC1, ERCC2 and RRM1 genes and chemosensitivity to cisplatin, carboplatin or gemcitabine.
  
  
  CONCLUSIONS
  These in vitro results suggest that further studies are needed to evaluate the expression of the RRM1, ERCC1 and ERCC2 genes as predictive biomarkers for sensitivity to platinum agents and gemcitabine.
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shimizu
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D004720:Endonucleases / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D051759:Xeroderma Pigmentosum Group D Protein / Q000096:biosynthesis*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D016190:Carboplatin; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin; D000093542:Gemcitabine