Resistance of human larynx carcinoma cells to cisplatin, gamma-irradiation and methotrexate does not involve overexpression of c-myc or c-Ki-ras oncogenes.
In our previous study, we achieved resistance to cisplatin or vincristine (VCR) by repeated treatments of human larynx carcinoma HEp2 cells with these drugs. Resistant cells were cloned and four clones were selected: CA3 and VA3 clones were selected from cells acutely treated with cisplatin or VCR, while CK2 and VK2 cells were selected from cells chronically treated with cisplatin and VCR, respectively. The aim of this study was to examine whether the development of resistance to cisplatin and vincristine changes the expression of c-myc and c-Ki-ras oncogenes and to determine whether there is a correlation between the expression of these oncogenes and the sensitivity of selected clones to cisplatin, methotrexate and gamma-rays. The cell sensitivity to cisplatin, methotrexate and gamma-rays was determined on the basis of the clonogenic survival assay. The expression of c-myc and c-Ki-ras oncogenes was examined by the use of RNA dot blot and Northern blot analyses. The results show that the development of resistance to selected drugs does not alter the expression of either c-myc or c-Ki-ras oncogene. CA3 and CK2 clones were resistant to cisplatin, while the vincristine resistant clones VA3 and VK2 became sensitive to this drug. The sensitivity of resistant clones to gamma-rays varied. CA3 cells were resistant, VA3 and VK2 cells sensitive, while CK2 cells exhibited the same sensitivity to gamma-rays as did the parental cells. All four clones tested became cross-resistant to methotrexate. We can conclude that development of resistance to cisplatin and vincristine does not alter the expression of c-myc or c-Ki-ras oncogene. We did not find any correlation between expression of these oncogenes and the sensitivity to cisplatin, methotrexate or gamma-rays.
Osmak
M
M
Ruder Bosković Institute, Department of Molecular Medicine, Zagreb, Croatia.
Beketić-Oresković
L
L
Matulić
M
M
Sorić
J
J
D015152:Blotting, Northern; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005720:Gamma Rays; D015870:Gene Expression; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008727:Methotrexate / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D012334:RNA, Neoplasm; D014750:Vincristine; D002945:Cisplatin; D008727:Methotrexate