Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1999 Nov 26;274(48):34141-7.

Overexpression of cyclooxygenase-2 induces cell cycle arrest. Evidence for a prostaglandin-independent mechanism.

Author information

  • 1Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06030-3505, USA.

Abstract

The immediate-early gene cyclooxygenase 2 (Cox-2) is induced in a variety of hyperplastic pathological conditions, including rheumatoid arthritis and colorectal cancer. Although a causal role for Cox-2 has been proposed, mechanisms by which Cox-2 function contributes to the pathogenesis of hyperplastic disease are not well defined. We constructed a green fluorescent protein-tagged Cox-2 (Cox-2-GFP) to examine its effects on a variety of cell types upon overexpression. Subcellular localization and enzymatic and pharmacological properties of Cox-2-GFP polypeptide were indistinguishable from those of the wild-type Cox-2 polypeptide. Overexpression of the Cox-2-GFP or the Cox-2 polypeptide by transient transfection suppressed the population of cells in the S phase of the cell cycle, with a concomitant increase in G(0)/G(1) population. In contrast, transient overexpression of GFP had no effect on cell cycle distribution, whereas endoplasmic reticulum-retained GFP (GFP-KDEL) overexpression was associated with only a minor decrease of cells in S phase. Interestingly, neither NS-398 (a Cox-2-specific inhibitor) nor indomethacin could reverse the effect of Cox-2-GFP overexpression on cell cycle progression. Furthermore, two mutants of Cox-2, S516Q and S516M, which lack the cyclooxygenase activity, exhibited the same effect as Cox-2-GFP. The cell cycle effect of Cox-2-GFP was observed in ECV-304, NIH 3T3, COS-7, bovine microvascular endothelial cells, and human embryonic kidney 293 cells. These findings suggest that Cox-2 inhibits cell cycle progression in a variety of cell types by a novel mechanism that does not require the synthesis of prostaglandins.

PMID:
10567385
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center