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Cell Growth & Differentiation Vol. 10, 537-544, August 1999
© 1999 American Association for Cancer Research

The Inhibitory Effects of Transforming Growth Factor ß1 on Breast Cancer Cell Proliferation Are Mediated through Regulation of Aberrant Nuclear Factor-{kappa}B/Rel Expression1

Mika A. Sovak, Marcello Arsura, Gregory Zanieski, Kathryn T. Kavanagh and Gail E. Sonenshein2

Departments of Pathology and Laboratory Medicine [M. A. S., K. T. K.] and Biochemistry [M. A., G. Z., G. E. S.], and Program in Research on Women’s Health [M. A. S., M. A., G. Z., K. T. K., G. E. S.], Boston University Medical School, Boston, Massachusetts 02118

Nuclear factor (NF)-{kappa}B/Rel transcription factors normally exist in non-B cells, such as epithelial cells, in inactive forms sequestered in the cytoplasm with specific inhibitory proteins, termed I{kappa}Bs. Recently, however, we discovered that breast cancer is typified by aberrant constitutive expression of NF-{kappa}B/Rel factors. Because these factors control genes that regulate cell proliferation, here we analyzed the potential role of NF-{kappa}B/Rel in the ability of transforming growth factor (TGF)-ß1 to inhibit the growth of breast cancer cells. The decreased growth of Hs578T and MCF7 breast cancer cell lines on TGF-ß1 treatment correlated with a drop in NF-{kappa}B/Rel binding. This decrease was due to the stabilization of the inhibitory protein I{kappa}B-{alpha}. Ectopic expression of c-Rel in Hs578T cells led to the maintenance of NF-{kappa}B/Rel binding and resistance to TGF-ß1-mediated inhibition of proliferation. Similarly, expression of the p65 subunit ablated the inhibition of Hs578T cell growth mediated by TGF-ß1. Thus, the inhibition of the aberrantly activated, constitutive NF-{kappa}B/Rel plays an important role in the arrest of the proliferation of breast cancer cells, which suggests that NF-{kappa}B/Rel may be a useful target in the treatment of breast cancer.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.