The most ominous development in
tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a
tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique panel of human DU145
prostate cancer sublines that vary in their invasive potential. The three DU145 sublines expressed
epidermal growth factor (
EGF) receptors that differed in their ability to activate
phospholipase C-gamma (
PLC gamma). Three-way analyses yielded 11 genes out of 4608 genes screened that associated directly or inversely with invasive potential. The gene whose expression correlated most strongly with lack of invasion was identified as a potential invasion suppressor and called prostin-1. Pharmacological inhibition of
PLC gamma (
U73122) confirmed that
PLC gamma signaling suppressed prostin-1 in that
U73122 treatment caused induction of prostin-1 in
PLC gamma competent cells. The prostin-1 gene, conserved through phylogeny, is induced by
androgen in LNCaP cells and encodes a 92
amino acid protein. The
protein shares no extensive homologies with other known genes, yet was recently identified as a small stabilizer subunit of the
dolichol-
phosphate-
mannose (DPM) synthase complex. That DPM3/prostin-1 might suppress
tumor progression was supported by the finding that exogenous expression in COS cells leads to apoptosis. These findings support the use of model cell lines to identify putative
tumor suppressors and promoters.