Oncogene overexpression and de novo drug-resistance in human prostate cancer cells.
We have isolated a variant [PC3(R)] of the human prostate PC3 tumor cell line which showed resistance to several anticancer drugs. Studies to evaluate the mechanisms of resistance to anticancer drugs in the PC3(R) cell line indicated that mdr1 was not overexpressed. Studies also indicated that activities of topo I and topo II were not different in these cell lines, nor was there any difference in the formation of drug-induced KCl-SDS precipitable complexes, indicating that topoisomerases were not involved in the development of resistance in PC3(R) cells. While the activity of glutathione S-transferase and total glutathione levels were also similar in these cell lines, the glutathione peroxidase activity in PC3(R) cells was 5-fold lower than in PC3 cells. Furthermore, proto-oncogene expression for c-jun, c-myc, and H-ras was significantly higher in resistant cells than in sensitive cells, indicating that the amplification of early response genes may play a role in the emergence of de novo resistance in PC3(R) cells.
Yamazaki
H
H
Biochemical & Molecular Pharmacology Section, NCI, NIH, Bethesda, MD 20892.
Schneider
E
E
Myers
C E
CE
Sinha
B K
BK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004351:Drug Resistance; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D011905:Genes, ras; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008297:Male; D009857:Oncogenes; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D005979:Glutathione Peroxidase; D004264:DNA Topoisomerases, Type I