Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-gamma regulated gene negatively associated with prostate tumor invasion

The most ominous development in tumor progression is the transition to an i nvasive and metastatic phenotype, Little is known, however, about the molec ular alterations that cause a tumor to become invasive, in view of this, we have used microarray expression analysis to evaluate the expression profil es of a unique panel of human DU145 prostate cancer sublines that vary in t heir invasive potential, The three DU145 sublines expressed epidermal growt h factor (EGF) receptors that differed in their ability to activate phospho lipase C-gamma (PLC gamma). Three-way analyses yielded 11 genes out of 4608 genes screened that associated directly or inversely with invasive potenti al, The gene whose expression correlated most strongly with lack of invasio n was identified as a potential invasion suppressor and called prostin-1. P harmacological inhibition of PLC gamma (U73122) confirmed that PLC gamma, s ignaling suppressed prostin-1 in that U73122 treatment caused induction of prostin-1 in PLC gamma, competent cells, The prostin-l gene, conserved thro ugh phylogeny, is induced by androgen in LNCaP cells acid encodes a 92 amin o acid protein, The protein shares no extensive homologies with other known genes, yet was recently identified as a small stabilizer subunit of the do lichol-phosphate-mannose (DPM) synthase complex, That DPM3/prostin-1 might suppress tumor progression was supported by the finding that exogenous expr ession in COS cells leads to apoptosis, These findings support the use of m odel cell lines to identify putative tumor suppressors and promoters.