HER2 Support Group Forums - View Single Post - The traditional diet of Greece and cancer.

R.B. · 09-17-2009, 01:51 PM

http://en.wikipedia.org/wiki/Plasmin...or_inhibitor-1
http://en.wikipedia.org/wiki/Plasmin

I have not seen this mechanism before and know nothing about it, but in general terms it appears to be another mechanism by which Omega 6 increases the risk of BC.

PAI-1 apparently is a poor prognostic factor for BC and is induced by Omega 6 in the cell line examined.

http://serpins.med.unc.edu/~fcc/Rese...erBiology.html (re article in general terms Omega 6 is a much stronger promoter of PPAR gamma than Omega 3 is. OMega 3 is more strongly associated with PPAR alpha)

http://breastcancer.about.com/od/dia...f/upa_pai1.htm

Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4.
Byon CH, Hardy RW, Ren C, Ponnazhagan S, Welch DR, McDonald JM, Chen Y.

Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA.

Obesity is a risk factor for breast cancer and is associated with increased plasma concentrations of free fatty acids (FFAs). We and others have demonstrated that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic marker for breast cancer. Therefore, we hypothesized that FFAs might increase expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231 cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs with different saturation and chain lengths, we demonstrated that linoleic acid induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell migration was completely inhibited by virally expressed antisense PAI-1 RNA. Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4-deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1 expression in breast cancer cells through SMAD4 provides a novel insight into understanding the relationships between two migration-associated molecules, FFAs, and PAI-1.Laboratory Investigation advance online publication, 14 September 2009; doi:10.1038/labinvest.2009.97.

09-17-2009, 01:51 PM	#314
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Re: The traditional diet of Greece and cancer. http://en.wikipedia.org/wiki/Plasmin...or_inhibitor-1 http://en.wikipedia.org/wiki/Plasmin I have not seen this mechanism before and know nothing about it, but in general terms it appears to be another mechanism by which Omega 6 increases the risk of BC. PAI-1 apparently is a poor prognostic factor for BC and is induced by Omega 6 in the cell line examined. http://serpins.med.unc.edu/~fcc/Rese...erBiology.html (re article in general terms Omega 6 is a much stronger promoter of PPAR gamma than Omega 3 is. OMega 3 is more strongly associated with PPAR alpha) http://breastcancer.about.com/od/dia...f/upa_pai1.htm Free fatty acids enhance breast cancer cell migration through plasminogen activator inhibitor-1 and SMAD4. Byon CH, Hardy RW, Ren C, Ponnazhagan S, Welch DR, McDonald JM, Chen Y. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA. Obesity is a risk factor for breast cancer and is associated with increased plasma concentrations of free fatty acids (FFAs). We and others have demonstrated that FFA induces plasminogen activator inhibitor-1 (PAI-1) expression in a variety of cells. Emerging evidence supports elevation of PAI-1 as a prognostic marker for breast cancer. Therefore, we hypothesized that FFAs might increase expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. Secreted PAI-1 was higher in invasive and metastatic MDA-MB-231 cells compared with less invasive and non-metastatic Hs578T cells. Utilizing FFAs with different saturation and chain lengths, we demonstrated that linoleic acid induced expression of PAI-1 in MDA-MB-231 cells. Linoleic acid also induced in vitro migration of MDA-MB-231. By contrast, other FFAs tested had little or no effect on PAI-1 expression or migration. Linoleic acid-induced breast cancer cell migration was completely inhibited by virally expressed antisense PAI-1 RNA. Furthermore, increased expression of PAI-1 by FFAs was not detected in the SMAD4-deficient MDA-MB-468 breast carcinoma cells. Electrophoretic mobility-shift assay confirmed that linoleic acid-induced expression of PAI-1 was mediated, at least in part, by SMAD4 in MDA-MB-231 cells. That linoleic acid induces PAI-1 expression in breast cancer cells through SMAD4 provides a novel insight into understanding the relationships between two migration-associated molecules, FFAs, and PAI-1.Laboratory Investigation advance online publication, 14 September 2009; doi:10.1038/labinvest.2009.97. Last edited by R.B.; 09-17-2009 at 02:05 PM..