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Volume 271, Number 45, Issue of November 8, 1996 pp. 28181-28188
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Role of Interferon Regulatory Factor-1 in the Induction of Biliary Glycoprotein (Cell CAM-1) by Interferon-

(Received for publication, June 17, 1996, and in revised form, August 6, 1996)

From the Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010

Biliary glycoprotein (BGP), also known as C-CAM-1, has been shown to be down-regulated in colon and prostate tumors. Previously, we demonstrated that BGP mRNA is up-regulated by interferon- (IFN-) in colon cancer cell lines (Takahashi, H., Okai, Y., Paxton, R. J., Hefta, L. J. F., and Shively, J. E. (1993) Cancer Res. 53, 1612-1619). We now show that the BGP promoter contains an interferon-sensitive response element (ISRE) that is specifically protected in in vivo footprints. Interferon regulatory factor-1 (IRF-1) was identified as the ISRE-binding factor by electrophoretic mobility shift assays. The induction of IRF-1 mRNA by IFN- in HT-29 cells reaches a maximum at 6 h and is superinduced by cycloheximide. Four mRNA species for BGP are induced by IFN-, the major band of which is inhibited by cycloheximide. Transfection of HT-29 cells with an IRF-1 expression plasmid (pAct-1) transactivates a BGP promoter reporter gene containing wild-type (but not mutant) ISRE. Electrophoretic mobility shift assay analysis of a second footprint reveals the binding of Sp1, an Sp1-like protein, and upstream stimulatory factor. The Sp1-like complex was also induced by IFN- treatment of HT-29 cells and may be a second point of transcriptional control for the BGP gene.

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