JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
RETRACTED PUBLICATION
Add like
Add dislike
Add to saved papers

Transforming growth factor-beta (TGF-beta) activates cytosolic phospholipase A2alpha (cPLA2alpha)-mediated prostaglandin E2 (PGE)2/EP1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)/Smad signaling pathways in human liver cancer cells. A novel mechanism for subversion of TGF-beta-induced mitoinhibition.

Transforming growth factor-beta (TGF-beta) potently inhibits the growth of human epithelial cells. However, neoplastic epithelial cells become resistant to TGF-beta-mediated mitoinhibition, and the mechanisms for this alteration during tumorigenesis are not fully understood. This study was designed to determine whether there is an association between the cytosolic phospholipase A2alpha (cPLA2alpha)-controlled eicosanoid metabolism and the growth response to TGF-beta in human liver cancer cells. TGF-beta treatment induced simultaneous Smad-mediated gene transcription and phosphorylation of cPLA2alpha. Whereas Smad activation inhibited tumor cell growth, phosphorylation of cPLA2 alpha promoted growth and counteracted Smad-mediated mitoinhibition. TGF-beta1 failed to prevent the growth of cells with high basal expression of cPLA2alpha, but inhibition of cPLA2 alpha, cyclooxygenase-2 (COX-2), or EP1 receptor restored mitoinhibition by TGF-beta1 in these cells. These results suggest that resistance of tumor cells to TGF-beta-mediated mitoinhibition involves activation of cPLA2alpha/COX-2/EP1 signaling. Furthermore, the TGF-beta1-induced Smad transcriptional activity and mitoinhibition were blocked by overexpression of cPLA2alpha or peroxisome proliferator-activated receptor-gamma (PPAR-gamma) but enhanced by depletion of cPLA2alpha or PPAR-gamma. These findings, along with the observations that cPLA2alpha activates PPAR-gamma and that PPAR-gamma binds Smad3, illustrate novel cPLA2alpha/COX-2/EP1 and cPLA2alpha/PPAR-gamma/Smad signaling pathways that counteract the mitoinhibition by TGF-beta in human cancer cells.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app