BACKGROUND. Oncoprotein 18 (op18) was first isolated as a molecule overexpr
essed in several malignant cells, suggesting a function of op18 in malignan
t processes, such as differentiation in hematologic malignancies, op18 also
was found to enhance microtubule deassembly in the cells. Antimitotic agen
ts that bind to tubulin have been used for chemotherapy to treat solid tumo
rs, such as lung carcinoma. Vinca alkaloids, such as vindesine and vincrist
ine, have commonly been used for chemotherapy of nonsmall cell lung carcino
ma. 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 vind
esine and vincristine, but not to taxanes. Vindesine-exposure increased the
G2/M population of the cell cycle in the Mock transfectants, but not in SB
C-3/op1, suggesting that the cell cycle dynamics were altered by op18 expre
ssion in SBC-3/op1.
CONCLUSION, Oncoprotein 18 expression is associated with lung carcinoma cel
l sensitivity to vindesine and may be able to serve as a surrogate marker f
or the chemosensitivity to Vinca alkaloids in human lung carcinomas. Cancer
2001;91: 1494-9. (C) 2001 American Cancer Society.