Transcriptional upregulation of interferon-induced protein kinase, PKR, in breast cancer.
PKR (double-stranded RNA activated protein kinase) is overexpressed and overactive in human breast carcinoma (BC) cells. Here, we report that BC cells also have higher PKR mRNA levels and exhibit increased transcription from the PKR promoter. Mutational analysis of the PKR promoter indicated that the interferon stimulation response element (ISRE) is responsible for the increased transcription in BC cells. By gel retardation assay, ISRE-protein complexes formed by BC and non-transformed nuclear extracts were compared. A BC-specific ISRE-protein complex resembles the multimeric factor, ISGF3.
Nussbaum
Jean M
JM
Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, MSB, E609, 185 South Orange Avenue, Newark NJ 07103-2714, USA.
Major
Marian
M
Gunnery
Shobha
S
D001943:Breast Neoplasms / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D012333:RNA, Messenger; D014157:Transcription Factors; D019892:eIF-2 Kinase