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- _5 label "Selventa" provenance.
- large_corpus.bel rights "Copyright (c) 2011-2012, Selventa. All rights reserved." provenance.
- _4 value "Mechanisms of cancer promotion by COX-2 are not fully understood, but signaling through prostaglandin (PG)E2 receptors is a contributing factor. The major PGE2 receptors on epithelial cells, EP2 and EP4, increase cAMP production, which promotes growth and inhibits apoptosis in some cell types. To explore the hypothesis that PGE2-stimulated cAMP is a key intracellular mediator of COX-2-dependent antiapoptosis and define the underlying mechanisms, we used the T84 human colon epithelial cell line, which exhibits inducible apoptosis and is responsive to PGE2 stimulation (31, 34, 35). The major PGE2 receptors on colon epithelial cells are EP2 and EP4 (25), a finding we confirmed by RT-PCR of T84 cells (data not shown). Both EP2 and EP4 receptors activate adenylyl cyclase and increase cAMP as a second messenger, suggesting that cAMP mediates antiapoptotic functions in epithelial cells. Consistent with this idea, we found that a membrane-permeant cAMP analog, 8-CPT-cAMP, and CTX, which catalyzes the ADP-ribosylation of Gs regulatory protein, leading to the activation of adenylyl cyclase, also inhibited Fas- and staurosporine-promoted apoptosis (Fig. 1 A). These findings were confirmed by evidence that CTX and 8-CPT-cAMP also inhibited the formation of apoptosis-associated DNA laddering in T84 cells (Fig. 1B and data not shown). We obtained similar results with the normal rat intestinal epithelial cell line, RIE-1 (Fig. 1C). Thus, the antiapoptotic response to increases in cAMP in intestinal epithelial cells is independent of their state of transformation and conserved across at least two species.\"From full text\"" provenance.
- _4 wasQuotedFrom 12837940 provenance.
- assertion hadPrimarySource 12837940 provenance.
- large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
- large_corpus.bel description "Approximately 61,000 statements." provenance.
- assertion wasDerivedFrom large_corpus.bel provenance.
- assertion wasDerivedFrom _4 provenance.
- large_corpus.bel authoredBy _5 provenance.
- large_corpus.bel version "20131211" provenance.