Messenger RNA expression of resistance factors in human tumor cell lines after single exposure to radiation.
Resistance of tumor cells to chemotherapeutic drugs can not only be caused by treatment with antineoplastic agents but also by radiotherapy. The aim of this study was to analyze whether ionizing radiation can influence the mRNA expression of proteins which have been found to be involved in drug resistance of tumor cells. Human tumor cell lines (MCF-7, LXF and Sk-Mel) were treated with single doses of irradiation (5, 10 and 20 Gy). The expression of the resistance related proteins glutathione S-transferase-pi (GST-pi), topoisomerase II alpha (Topo II), thymidylate synthase (TS), O6-methylguanine-DNA-methyltransferase (MGMT), P-glycoprotein (Pgp), glutathione peroxidase (GPX) multidrug resistance-associated protein (MRP) and also of the heat-shock protein 70 (HSP 70) were determined at the mRNA level during the time interval from 1.5 to 72 h post-irradiation and compared with their corresponding controls. We also examined whether a relationship exists between these proteins and the proliferative activity (histone 3, Ki-67, statin) of the cells. We found that exposure of MCF-7, LXF and Sk-Mel cells to ionizing radiation increases the expression of the mRNA of GST-pi. Topo II, TS, HSP 70 and proliferation markers were also altered by exposure to ionizing radiation, but there was no common response of the three cell lines. No significant changes were observed in the expression of MGMT, Pgp, GPX and MRP after radiation treatment. Drug resistance tests revealed that irradiated MCF 7 cells were less sensitive to doxorubicin than non-irradiated control cells. Our results indicate that ionizing irradiation modifies the expression of some proteins involved in drug resistance and the response of MCF 7 cells to doxorubicin and may, therefore, play a role in clinical drug response.
Stammler
G
G
German Cancer Research Center, Heidelberg, Germany.
Pommerenke
E W
EW
Masanek
U
U
Mattern
J
J
Volm
M
M
D015152:Blotting, Northern; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000528:radiation effects*; D004798:Enzymes / Q000096:biosynthesis / Q000235:genetics; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured
D004798:Enzymes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm