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Cell Growth & Differentiation Vol. 10, 457-465, July 1999
© 1999 American Association for Cancer Research

Retinoblastoma Protein Expression Leads to Reduced Oct-1 DNA Binding Activity and Enhances Interleukin-8 Expression1

Hongquan Zhang, Alexander T. Shepherd, Donna D. Eason, Sheng Wei, Jose I. Diaz, Julie Y. Djeu, Gary D. Wu and George Blanck2

Departments of Pathology and Laboratory Medicine [H. Z., J. I. D.] and Biochemistry and Molecular Biology [A. T. S., D. D. E., G. B.], College of Medicine, and Immunology Program [S. W., J. Y. D., G. B.], H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, and Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 [G. D. W.]

Tumor cell lines with a defective retinoblastoma gene are unable to transcribe the HLA class II genes in response to IFN-{gamma} treatment, and reconstitution of functional Rb rescues IFN-{gamma}-induced class II gene expression. However, the molecular mechanism of Rb rescue of the class II genes is unknown. We have examined the effect of Rb expression on the activation of the promoter for HLA-DRA, the prototype class II gene. Oct-1, a POU domain transcription factor, was identified as a repressor of HLA-DRA promoter activity in the Rb-defective cells. Rb expression led to phosphorylation of Oct-1, thus relieving its repressive effect. Oct-1 has also been shown to repress interleukin 8 promoter activity. Consistent with reduced levels of Oct-1 DNA binding activity in the Rb-transformed cell lines, interleukin 8 expression is higher in these cell lines.




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Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.