CORRELATIONS BETWEEN INTRINSIC CHEMORESISTANCE AND HER-2 NEU GENE-EXPRESSION, P53 GENE-MUTATIONS, AND CELL-PROLIFERATION CHARACTERISTICS INNON-SMALL-CELL LUNG-CANCER CELL-LINES/

Using a panel of 20 non-small cell lung cancer (NSCLC) ceh lines estab lished from previously untreated patients, we investigated the relatio nships between intrinsic chemoresistance (to four agents used commonly in the therapy of NSCLC) and HER-2/neu gene expression (which encodes glycoprotein p185(neu)), p53 gene mutations, and cell proliferation c haracteristics. Our results demonstrated that high p185(neu) expressio n was correlated with chemoresistance, low S-phase fractions, and long doubling times. By contrast, cell lines expressing relatively low lev els of p185(neu) were relatively chemosensitive and had higher S-phase fractions and shorter doubling times. Although mutation of the p53 ge ne was a common event in this panel of cell lines (present in 18 of 20 lines), there was no relationship between mutations at any specific c odon and chemoresistance or cell proliferation characteristics. Multiv ariate analysis revealed that the level of p185(neu) was the only inde pendent predictor for chemoresistance to doxorubicin, etoposide, and p robably cisplatin. Although intrinsic chemoresistance almost certainly is a multifactorial process, overexpression of p185(neu) may be an im portant factor in the chemoresistance of NSCLC.