Resistance to hydrogen peroxide associated with altered catalase mRNA stability in MCF7 breast cancer cells.
We have established a variant of the human breast cancer cell line MCF7, designated MCF7/H2O2, which is 5-fold resistant to H2O2 by clonogenic assay. The specific activity of the H2O2 disposal enzyme catalase was elevated 3-fold in MCF7/H2O2; activities of other antioxidant enzymes, including glutathione peroxidase and superoxide dismutase, were not increased. The steady-state level of catalase mRNA was only slightly elevated (approx. 1.6-fold) in MCF7/H2O2 cells; however, degradation of catalase mRNA was markedly retarded in MCF-7/H2O2 compared to MCF-7 (82% of catalase mRNA remained 24 h after inhibition of RNA synthesis by actinomycin D in MCF-7/H2O2 vs. 32% in MCF7). The degradation rates of superoxide dismutase mRNA and 28 S ribosomal RNA were not reduced in MCF-7/H2O2; however, the rate of degradation of another mRNA species, beta-actin, was also significantly decreased. These data suggest that resistance to H2O2 in MCF7/H2O2 cells is mediated by elevated catalase activity which can be explained by stabilization of certain mRNA species, including catalase mRNA.
Akman
S A
SA
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010.
Forrest
G
G
Chu
F F
FF
Doroshow
J H
JH
D000199:Actins / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology*; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004351:Drug Resistance; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000199:Actins; D012333:RNA, Messenger; D003609:Dactinomycin; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase