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| Content Provider | Springer Nature Link |
|---|---|
| Author | Joseph, R. R. Yazer, E. Hanakawa, Y. Stadnyk, A. W. |
| Copyright Year | 2005 |
| Abstract | Recent data indicates that chronic inflammation of the intestine such as Crohn's or ulcerative colitis puts those individuals at heightened risk for colorectal adenocarcinoma. In this study, we examine the effect of the inflammatory mediator PGE2 and associated signalling on detachment-induced cell death (anoikis) in intestinal epithelial cells. Treatment of detached IEC-18 with 0.01–0.05 μM PGE2 increased cell viability as well as induced aggregation. As EP4 prostaglandin receptors on IEC are coupled to adenylate cyclase, we next treated cells with agents that promote cAMP signalling (Forskolin, dbcAMP, and etazolate), all of which promoted IEC aggregation as well as survival. We next treated detached IECs with specific inhibitors of adenylate cyclase or PKA, which accelerated anoikis. To explore the mechanism of cell-cell adhesion, we next treated detached IECs with an anti-E-cadherin blocking antibody which dispersed aggregates induced by dbcAMP, and an adenovirus expressing a dominant negative E-cadherin (EcadΔEC) prevented aggregate formation. Interestingly EcadΔEC prevented aggregation of IEC induced by dbcAMP but did not significantly reduce viability. This suggests that cAMP signalling is important in both aggregate formation and promoting viability but these are distinct events. Taken together, these data support a mechanism whereby elevated PGE2 levels characteristic of colitis prevent anoikis by activating an AC-, cAMP-, and PKA-dependent signalling pathway. The delay of apoptosis by PGE2 may be one mechanism by which inflammation may contribute to carcinogenesis. |
| Starting Page | 1221 |
| Ending Page | 1233 |
| Page Count | 13 |
| File Format | |
| ISSN | 13608185 |
| Journal | Apoptosis |
| Volume Number | 10 |
| Issue Number | 6 |
| e-ISSN | 1573675X |
| Language | English |
| Publisher | Kluwer Academic Publishers |
| Publisher Date | 2005-10-03 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | anoikis cancer epithelium inflammation intestine prostaglandin Cancer Research Virology Oncology Biochemistry Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology |
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