A distinct kinase modulates the expression of IFN-inducible genes in human breast cancer cells.
The biological activity of interferons (IFNs) is presumed to be mediated through the induction of a number of IFN-inducible genes. IFN-mediated gene induction was examined in two human breast cancer cell lines, MCF-7 and BT-20. Both these cell lines were remarkably responsive to IFNs as a number of IFN inducible genes were rapidly induced. We examined the sensitivity of these genes towards 2-aminopurine (2-AP), a known inhibitor of double-stranded (ds) RNA dependent protein kinase. 2-AP has also been reported to inhibit the induction of IFN-beta 1 in response to dsRNA and the genes c-myc and c-fos in fibroblasts. In both MCF-7 and BT-20 cell lines, 2-AP selectively inhibited the IFN-induced gene responses. 2-AP did not affect levels of the oncogene, HER-2/neu. Tamoxifen (TAM), an antiestrogenic drug, which is known to inhibit the activity of protein kinase C at high concentrations, did not affect IFN-mediated gene induction. Our data is consistent with the concept that the 2-AP sensitive kinase is primarily associated with the IFN-induced gene systems and that positive and negative growth regulating stimuli in breast cancer may require the participation of distinct kinases.
Tiwari
R K
RK
Breast Cancer Research Laboratory, Memorial Sloan Kettering Cancer Center, New York, N.Y. 10021.
Osborne
M P
MP
D015075:2-Aminopurine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D010770:Phosphotransferases / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen / Q000494:pharmacology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D015075:2-Aminopurine; D004967:Estrogens; D007370:Interferon Type I; D007372:Interferons; D009856:Oncogene Proteins, Viral; D010770:Phosphotransferases; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen