Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines.
OBJECTIVE
RanBP2 is a small ubiquitin-like modifier ligase for DNA topoisomerase II (TopoII) and plays a role in maintaining chromosome stability by recruiting TopoII to centromeres during mitosis. Engineered-mice with low amounts of RanBP2 have been reported to form lung adenocarcinomas. Furthermore, in the murine embryonic fibroblasts, formation of chromatin bridges in anaphase, a distinctive feature of cells with impaired DNA decatenation by chemical inhibition of TopoII, has been reported. In this study, we tested whether the association between mRNA expression of the RanBP2 gene and chemosensitivity of a TopoII inhibitor, amrubicin could be seen.


METHODS
Using a panel of 20 lung cancer cell lines, the mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes were examined by quantitative real-time reverse transcription PCR. The in vitro cytotoxicity of amrubicin was assessed using a tetrazolium-based colorimetric assay (MTT assay).


RESULTS
Although RanBP2 mRNA expression was infrequently downregulated in human lung cancer cell lines, significantly higher RanBP2 transcripts were observed in small cell lung cancer than non-small cell lung cancer. There were no correlations between chemosensitivity of amrubicin and mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes.


CONCLUSIONS
Our in vitro results suggest that mRNA expressions of RanBP2 and TopoII isoforms are unlikely to be a predictive biomarker for the sensitivity to amrubicin.
Horio
Yoshitsugu
Y
Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. yhorio@aichi-cc.jp
Osada
Hirotaka
H
Shimizu
Junichi
J
Ogawa
Shizu
S
Hida
Toyoaki
T
Sekido
Yoshitaka
Y
D018943:Anthracyclines / Q000633:toxicity*; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D015415:Biomarkers; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D043171:Chromosomal Instability / Q000187:drug effects; D004396:Coloring Agents; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018832:Molecular Chaperones / Q000096:biosynthesis*; D028861:Nuclear Pore Complex Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004396:Coloring Agents; D007527:Isoenzymes; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C094493:ran-binding protein 2; C055866:amrubicin; D004250:DNA Topoisomerases, Type II; C022616:thiazolyl blue