Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells

Background: Hypertriglyceridemia was recently shown to be a risk factor for prostate cancer; however, there are only a few reports about the relationship between Prostate cancer and TG (triglycerides) rich lipoproteins. Remnant lipoproteins (RLP) are TG-rich lipoproteins, which are produced by the hydrolysis of very low density lipoproteins and chylomicrons. We examined the direct effect of RLP on the proliferation and signal transduction of prostate cancer cells. Methods: RLP were isolated from human serum with an immunoaffinity mixed gel containing anti-apoA-1 and anti-apoB-100. We evaluated RLP-induced cell proliferation by using NITS assay. Moreover we examined the direct effect of RLP on the MAPK and Akt signal transductions which are reported to be correlated with prostate cancer by using Western blotting. Results: Incubation in the presence of RLP for 48 h induced the proliferation of prostate cancer PC-3 cells more significantly than prostate cancer LNCaP cells and human prostate stromal cells. In PC-3 cells, RLP also induced the phosphorylation of MEK/ERK via a G protein-coupled receptor-protein kinase C dependent pathway. Moreover, activation of Akt pathway was observed after RLP treatment of PC-3. Conclusion: These findings suggested that hypertriglyceridemia, especially remnant hyperlipoproteinemia, might be one of the progressive factors for prostate cancer. (C) 2007 Elsevier B.V. All rights reserved.