In vivo and in vitro regulation of syndecan 1 in prostate cells by n-3 polyunsaturated fatty acids.
Syndecan 1 is the major proteoglycan produced by epithelial cells. It is strategically localized at the plasma membrane to participate in growth factor signaling and cell-cell and cell-matrix interactions. Its expression may modulate the properties of epithelial lineage tumor cells in which it is generally down-regulated compared with nontumor progenitors. The present study examined the regulation of syndecan 1 in prostate epithelial cells by n-3 polyunsaturated fatty acids. In prostate tissue of mice, syndecan 1 immunostaining was demonstrated in epithelial cells throughout each gland. In animals fed an n-3 polyunsaturated fatty acid-enriched diet, syndecan 1 mRNA was increased in all prostate glands. In the human prostate cancer cell line, PC-3, delivery of exogenous n-3 (but not n-6) fatty acids resulted in up-regulation of syndecan 1 expression. This effect was mimicked by a peroxisome proliferator-activated receptor (PPAR) gamma agonist, troglitazone, and inhibited in the presence of a PPARgamma antagonist and in cells transfected with dominant negative PPARgamma cDNA. Using a luciferase gene driven either by a PPAR response element or by a DR-1 site present in the syndecan 1 promoter, reporter activation was increased by n-3 low density lipoprotein, docosahexaenoic acid, and troglitazone, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. These findings indicate that syndecan 1 is up-regulated by n-3 fatty acids by a transcriptional pathway involving PPARgamma. This mechanism may contribute to the chemopreventive properties of n-3 fatty acids in prostate cancer.
Edwards
Iris J
IJ
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. iedwards@wfubmc.edu
Sun
Haiguo
H
Hu
Yunping
Y
Berquin
Isabelle M
IM
O'Flaherty
Joseph T
JT
Cline
J Mark
JM
Rudel
Lawrence L
LL
Chen
Yong Q
YQ
D000818:Animals; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D053668:Syndecan-1 / Q000096:biosynthesis* / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology; D014018:Tissue Distribution; D000077288:Troglitazone
D002839:Chromans; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma; D012333:RNA, Messenger; D053668:Syndecan-1; D045162:Thiazolidinediones; D000077288:Troglitazone