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R.B. · 09-15-2008, 04:23 AM

PPAR gamma has made a previous appearance as having a link with BC. The trial below suggest that the products of oxidation of Omega 6 linoleic acid promote PPAR gamma which is suggested to be a tumour promoter in BC.

http://genesdev.cshlp.org/cgi/content/abstract/18/5/528

ABSTRACT

"These results suggest that once an initiating event has taken place, increased PPAR{gamma} signaling serves as a tumor promoter in the mammary gland."

http://carcin.oxfordjournals.org/cgi...act/24/11/1717

ABSTRACT

Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma}

Arthur W. Bull1,4, Knut R. Steffensen2, Jörg Leers2 and Joseph J. Rafter3

1 Oakland University, Department of Chemistry, Rochester MI 48309-4477, USA, 2 Center for Biotechnology, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden and 3 Department of Medical Nutrition, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden

The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) {gamma} plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for {gamma}1, {gamma}2 and {gamma}3, in Caco-2 and HCT-116 colon cell lines showed that {gamma}3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR {gamma} by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR {gamma}1 or {gamma}2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR {gamma} and that PPAR {gamma} plays an important role in the differentiation of intestinal cells.

09-15-2008, 04:23 AM	#265
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	PPAR gamma has made a previous appearance as having a link with BC. The trial below suggest that the products of oxidation of Omega 6 linoleic acid promote PPAR gamma which is suggested to be a tumour promoter in BC. http://genesdev.cshlp.org/cgi/content/abstract/18/5/528 ABSTRACT "These results suggest that once an initiating event has taken place, increased PPAR{gamma} signaling serves as a tumor promoter in the mammary gland." http://carcin.oxfordjournals.org/cgi...act/24/11/1717 ABSTRACT Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma} Arthur W. Bull1,4, Knut R. Steffensen2, Jörg Leers2 and Joseph J. Rafter3 1 Oakland University, Department of Chemistry, Rochester MI 48309-4477, USA, 2 Center for Biotechnology, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden and 3 Department of Medical Nutrition, Karolinska Institute, NOVUM, 141 86 Huddinge, Sweden The nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR) {gamma} plays an important role in the differentiation of intestinal cells and other tissues. Real-time PCR examination of PPAR mRNA for {gamma}1, {gamma}2 and {gamma}3, in Caco-2 and HCT-116 colon cell lines showed that {gamma}3 is the most abundant message in both lines. Treatment of Caco-2 cells with sodium butyrate, which induces cell differentiation, also leads to an increase in all three PPAR mRNAs. In contrast, treatment of HCT-116 cells with sodium butyrate, which does not lead to differentiation of these cells, causes a decrease in the amount of all three PPAR mRNAs. Furthermore, the amount of PPAR mRNA is greater in Caco-2 cells than in HCT-116 cells at all times examined. As several oxidative metabolites of linoleic acid, including 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO) have been shown to bind PPAR, and there is a strong positive correlation between enzymes for metabolism of linoleate oxidation products, intestinal cell differentiation and the distribution of PPAR, we also performed a detailed investigation of the activation of PPAR {gamma} by 13-HODE and 13-OXO. For these experiments, Caco-2 and HCT-116 cells were transfected with constructs containing PPAR {gamma}1 or {gamma}2 then a PPRE-luc reporter construct. Exposure of transfected cells to micromolar concentrations of 13-HODE or 13-OXO produced concentration-dependent increases in luciferase activity. In addition, the two linoleate metabolites activate endogenous PPAR in these cell lines transfected with only PPRE-luc. The data substantiate the contention that oxidation products of linoleic acid are metabolically produced endogenous ligands for PPAR {gamma} and that PPAR {gamma} plays an important role in the differentiation of intestinal cells.