Oncoprotein 18 overexpression increases the sensitivity to vindesine in the human lung carcinoma cells.
BACKGROUND
Oncoprotein 18 (op18) was first isolated as a molecule overexpressed in several malignant cells, suggesting a function of op18 in malignant processes, such as differentiation in hematologic malignancies, op18 also was found to enhance microtubule deassembly in the cells. Antimitotic agents that bind to tubulin have been used for chemotherapy to treat solid tumors, such as lung carcinoma. Vinca alkaloids, such as vindesine and vincristine, have commonly been used for chemotherapy of nonsmall cell lung carcinoma. The authors examined the role of op18 in the sensitivity of human lung carcinoma cells to antimitotic agents.


METHODS
Expression of op18 mRNA was detected in all 17 lung carcinoma cell lines tested by Northern blotting. Oncoprotein 18 cDNA was transfected to SBC-3 human lung carcinoma cells, and the stable transfectants, SBC-3/op1-3, were isolated. The sensitivity of these transfectants against antimitotic agents were examined by the MTT assay in vitro. Cell cycle distribution of the transfectants on DNA histogram was analyzed by flow cytometry.


RESULTS
Oncoprotein 18-transfected cells showed higher sensitivity to vindesine and vincristine, but not to taxanes. Vindesine-exposure increased the G2/M population of the cell cycle in the Mock transfectants, but not in SBC-3/op1, suggesting that the cell cycle dynamics were altered by op18 expression in SBC-3/op1.


CONCLUSIONS
Oncoprotein 18 expression is associated with lung carcinoma cell sensitivity to vindesine and may be able to serve as a surrogate marker for the chemosensitivity to Vinca alkaloids in human lung carcinomas.
Nishio
K
K
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan. knishio@gan2.res.ncc.go.jp
Nakamura
T
T
Koh
Y
Y
Kanzawa
F
F
Tamura
T
T
Saijo
N
N
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015152:Blotting, Northern; D002277:Carcinoma / Q000473:pathology*; D018076:DNA, Complementary; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008868:Microtubule Proteins; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D050777:Stathmin; D014162:Transfection; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology; D014751:Vindesine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D018076:DNA, Complementary; D008868:Microtubule Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D014750:Vincristine; D017239:Paclitaxel; D014751:Vindesine