HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/G263    most recent 00267.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, H. Articles by Houghton, J. Search for Related Content PubMed PubMed Citation Articles by Li, H. Articles by Houghton, J.

MUCOSAL BIOLOGY

Fas Ag-FasL coupling leads to ERK1/2-mediated proliferation of gastric mucosal cells

¹Department of Medicine, Division of Gastroenterology, and ²Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts

Submitted 13 June 2007 ; accepted in final form 2 November 2007

When cells within the gastric mucosa progress from metaplasia to dysplasia to cancer, they acquire a Fas Ag apoptosis-resistant phenotype. It is unusual to completely abolish the pathway, suggesting other forms of Fas Ag signaling may be important or even necessary for gastric cancer to progress. Little is known about alternate signaling of the Fas Ag pathway in gastric mucosal cells. Using a cell culture model of rat gastric mucosal cells, we show that gastric mucosal cells utilize a type II signaling pathway for apoptosis. Under conditions of low receptor stimulation or under conditions where apoptosis is blocked downstream of the death-inducing signal complex, Fas Ag signaling proceeds toward proliferative signaling. Under conditions favoring proliferative signaling, cFLIP is recruited to the Fas-associated death domain-like interleukin-1β-converting enzyme at the death-inducing signal complex and activates ERK1/2. ERK1/2 in turn activates NF-B. ERK1/2 stimulates proliferation, whereas NF-B activation results in upregulation of the antiapoptotic protein survivin, further promoting proliferation over apoptosis. These results suggest that factors that inhibit apoptosis confer a growth advantage to the cells beyond the survival advantage of avoiding apoptosis and in effect convert the Fas Ag signaling pathway from a tumor suppressor to a tumor promoter.

tumor promoter; cell culture; alternate signaling

This article has been cited by other articles:

				J. C. Symes, M. Kurin, N. E. Fleshner, and J. A. Medin Fas-mediated killing of primary prostate cancer cells is increased by mitoxantrone and docetaxel Mol. Cancer Ther., September 1, 2008; 7(9): 3018 - 3028. [Abstract] [Full Text] [PDF]