Does the PGC-1/PPARgamma pathway play a role in Com-1/p8 mediated cell growth inhibition in prostate cancer?
Com-1, candidate of metastasis-1, also known as p8, has been shown to regulate the growth and apoptosis of cancer cells and is associated with the disease progression in human cancers including prostate cancer. In the current study, we investigated a potential mechanism underlying the anticancer action of Com-1/p8 in human prostate cancer. Human prostate cancer cells were used. Full-length Com-1 cDNA was isolated from normal mammary tissues. Ribozyme transgenes that specifically target human Com-1 were constructed using the pEF6/V5-His vector. Com-1 interacting proteins were determined using immunoprecipitation method. Cell growth and invasiveness were investigated using in vitro methods. Using immunoprecipitation and Western blotting, Com-1 was found to be cross-reprecipitated with PGC-1, a coactivator of peroxisome proliferator activated receptor (PPAR)-gamma, but not PPAR-gamma itself. Elimination of Com-1 from prostate cancer cells resulted in a reduced response of the cells to ciglitizone, a PPAR-gamma agonist, whereas forced expression of Com-1 rendered cells more responsive to ciglitizone. We further demonstrated that the overexpression of Com-1/p8 resulted in changes in the expression of the PGC-1 responsive gene, fatty acid synthase (FAS). Com-1 may act as a tumour suppressor in human prostate cancer cells. The potential tumour suppressive effect of Com-1 is at least partly via its interaction with PGC-1, the PPAR-gamma coactivator.
Jiang
Wen G
WG
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff CF14 4XN, UK. jiangw@cf.ac.uk
Davies
Gaynor
G
Kynaston
Howard
H
Mason
Malcolm D
MD
Fodstad
Oystein
O
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018076:DNA, Complementary; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045162:Thiazolidinediones / Q000494:pharmacology; D019076:Transgenes
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; C491643:NUPR1 protein, human; C039671:ciglitazone