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Arkansas Children’s Nutrition Center and Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 1120 Marshall St, Little Rock, Arkansas 72202, USA

(Requests for offprints should be addressed to R C M Simmen; Email: simmenrosalia{at}uams.edu)

The over-expression of epidermal growth factor receptor (EGFR) and its ligands, epidermal growth factor (EGF) and transforming growth factor-, is a common feature of epithelial carcinomas and correlates with neoplastic progression. Secretory leukocyte protease inhibitor (SLPI), a member of the Kazal superfamily of serine anti-proteases, induces proliferation and promotes malignancy of epithelial cells and is expressed at high levels in multiple tumor types. In the present study, we have demonstrated that EGF increases SLPI expression in the human endometrial epithelial cell line Ishikawa in a dose- and time-dependent manner. We have shown that this effect of EGF occurs, in part, at the level of the SLPI promoter and involves the MAP kinase signaling pathway. We have further shown that EGF promotion of cell proliferation, but not induction of cyclin D1 gene expression, involves SLPI. Our results suggest that the regulation of SLPI expression by EGFR ligand(s) may represent a ‘feed-forward’ mechanism by which the enhanced proliferative and migratory properties of EGFR over-expressing cancer cells are sustained. Increased SLPI expression is likely an important component of altered EGFR signaling in human tumors and may have significant therapeutic implications in cancer progression.

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				F. A. Simpkins, N. M. Devoogdt, N. Rasool, N. E. Tchabo, E. U. Alejandro, M. M.R.N. Kamrava, and E. C. Kohn The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells Carcinogenesis, March 1, 2008; 29(3): 466 - 472. [Abstract] [Full Text] [PDF]

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