Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Activation of cPLA2 is required for leukotriene D4-induced proliferation in colon cancer cells.

In English

Författare

Summary, in English

It is well documented that prolonged inflammatory conditions, particularly those relating to the colon, have been shown to induce cancer. We have previously demonstrated that the pro-inflammatory mediator leukotriene D-4 (LTD4) induces survival and proliferation in intestinal cells and that its receptor, CysLT(1), is upregulated in human colon cancer tissue. Here we demonstrate, for the first time that in both Int 407 (a non-transformed human intestinal epithelial cell line) and Caco-2 cells (a human colorectal carcinoma cell line), cytosolic phospholipase A(2)alpha (cPLA(2)alpha) is activated and translocates to the nucleus upon LTD4 stimulation via a calcium-dependent mechanism that involves activation of protein kinase C (PKC), and the mitogen-activated protein kinases ERK1/2 and p38. We also show with a cPLA(2)alpha promoter luciferase assay, that LTD4 induces an increase in the transcriptional activity of cPLA(2)alpha via activation of cPLA(2)alpha and the transcription factor NF kappa B. Interestingly we demonstrate here that both the basal and the LTD4-induced cPLA(2)alpha activity is elevated similar to 3-fold in Caco-2 colon cancer cells compared with Int 407 cells. The difference in basal activity was confirmed in human colon tumor samples by the finding of a similar increase in cPLA(2)alpha activity when compared with normal colon tissue. A functional role of the increased cPLA(2)alpha activity in tumor cells was revealed by our findings that inhibition of this enzyme reduced both basal and LTD4-induced proliferation, the effects being most pronounced in Caco-2 tumor cells. The present data reveal that cPLA(2)alpha, an important intracellular signal activated by inflammatory mediators, is an important regulator of colon tumor growth.

Publiceringsår

2005

Språk

Engelska

Sidor

1988-1998

Publikation/Tidskrift/Serie

Carcinogenesis

Volym

26

Issue

Jun 23

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Cell Pathology, Malmö
  • Surgery

ISBN/ISSN/Övrigt

  • ISSN: 0143-3334