Linked Life Data

15254749

Source:http://linkedlifedata.com/resource/pubmed/id/15254749

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-15
pubmed:abstractText
Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in the control of cell proliferation, apoptosis and differentiation in various tumor cells. Among PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (PGJ2), the ultimate metabolite of PGD2, plays a role in the biology of brain tumors. It is still unclear to which extent the anti-proliferative and differentiation-promoting activity of PGJ2 is mediated through PPARgamma. We compared the effects of PGJ2 with those of rosiglitazone - the synthetic agonist with the highest affinity for PPARgamma - in 4 human glioblastoma cell lines (A172, U87-MG, M059K, M059J). All cell lines expressed high levels of PPARgamma, consistent with the high levels of PPARgamma protein in 5 tumor samples. Both PGJ2 and rosiglitazone inhibited proliferation of all cell lines with a G2/M arrest and apoptosis, but only PGJ2 up-regulated p21Cip/WAF1. The growth inhibitory effect was partially reversed by the PPARgamma antagonist GW9662. We studied the time sequence of selected molecular events, that lead glioblastoma cells to apoptosis and/or differentiation, after treatment with both agonists. M059K cells committed to undergo apoptosis by PGJ2, initially up-regulated PPARgamma, and then down-regulated PPARgamma as they began apoptosis. Apoptotic cells also increased their expression of retinoic acid receptor beta (RARbeta) and retinoid X receptor alpha (RXRalpha). PGJ2 increased expression of glial fibrillary acidic protein (GFAP) and decreased levels of vimentin, structural proteins modulated during astrocytic differentiation. Unexpectedly, PGJ2 up-regulated the expression of cyclooxygenase-2 (COX-2). Rosiglitazone caused the same pattern of PPARgamma, RARbeta and RXRalpha expression as PGJ2, but no significant modulation of p21Cip/WAF1, cytoskeletal proteins or COX-2 occurred. Our data indicate that PGJ2, and rosiglitazone suppress cell proliferation and cause apoptosis in glioblastoma cell lines, most likely through a PPARgamma-dependent pathway. By contrast, the modulation of differentiation-associated proteins by PGJ2, but not rosiglitazone, suggests that PGJ2 promotes differentiation of glioblastoma cells independently of PPARgamma activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/9-deoxy-delta-9-prostaglandin D2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Glial Fibrillary Acidic Protein, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neurofilament Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin D2, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases, http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/Vimentin, http://linkedlifedata.com/resource/pubmed/chemical/neurofilament protein NF 68, http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
493-502
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15254749-Apoptosis, pubmed-meshheading:15254749-Cell Differentiation, pubmed-meshheading:15254749-Cell Nucleus, pubmed-meshheading:15254749-Cell Proliferation, pubmed-meshheading:15254749-Cyclooxygenase 2, pubmed-meshheading:15254749-G2 Phase, pubmed-meshheading:15254749-Gene Expression, pubmed-meshheading:15254749-Glial Fibrillary Acidic Protein, pubmed-meshheading:15254749-Glioblastoma, pubmed-meshheading:15254749-Humans, pubmed-meshheading:15254749-Isoenzymes, pubmed-meshheading:15254749-Membrane Proteins, pubmed-meshheading:15254749-Neurofilament Proteins, pubmed-meshheading:15254749-PPAR gamma, pubmed-meshheading:15254749-Prostaglandin D2, pubmed-meshheading:15254749-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:15254749-Thiazolidinediones, pubmed-meshheading:15254749-Tumor Cells, Cultured, pubmed-meshheading:15254749-Up-Regulation, pubmed-meshheading:15254749-Vimentin
pubmed:year
2004
pubmed:articleTitle
The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines.
pubmed:affiliation
Division of Pediatric Oncology, Catholic University of Rome, 00168 Rome, Italy. rmorosetti@rm.unicatt.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't