Increased expression of T-plastin gene in cisplatin-resistant human cancer cells: identification by mRNA differential display.
The cellular resistance to the potent anticancer agent cis-diamminedichloroplatinum(II) (cisplatin) is thought to be mediated by multiple mechanisms. The technique of differential display of mRNAs was applied to various cisplatin-resistant cell lines and the corresponding parental sensitive human bladder, prostatic, and head and neck cancer cells in order to identify genes that underlie cisplatin resistance. Twenty-four clones were confirmed by Northern blot analysis to be expressed differentially between resistant and the corresponding sensitive cells. Partial DNA sequences of the eight clones that showed a threefold or greater increase in expression in either the resistant cells (seven clones) or sensitive cells (one clone) revealed that two were derived from the T-plastin gene and one from the tissue factor gene. The abundance of T-plastin mRNA in cisplatin-resistant T24/DDP10 cell was approximately 12 times that in the parental T24 cells. Transfection of T24/DDP10 cells with a vector encoding full-length T-plastin antisense RNA demonstrated that reduced T-plastin expression was associated with increased sensitivity to cisplatin. These results are consistent with the hypothesis that several mechanisms participate cooperatively in the acquisition of cisplatin resistance in human cancer.
Hisano
T
T
Department of Biochemistry, Kyushu University School of Medicine, Fukuoka, Japan.
Ono
M
M
Nakayama
M
M
Naito
S
S
Kuwano
M
M
Wada
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013925:Thromboplastin / Q000235:genetics; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C026742:plastin; D013925:Thromboplastin; D002945:Cisplatin