The Caenorhabditis elegans homolog of the putative prostate cancer susceptibility gene ELAC2, hoe-1, plays a role in germline proliferation

Abstract

The potential prostate cancer susceptibility gene ELAC2 has a Caenorhabditis elegans homolog (which we call hoe-1, for ẖomolog o̱f E̱LAC2). We have explored the biological role of this gene using RNAi to reduce gene activity. We found that worms subjected to hoe-1 RNAi are slow-growing and sterile. The sterility results from a drastic reduction in germline proliferation and cell-cycle arrest of germline nuclei. We found that hoe-1 is required for hyperproliferation phenotypes seen with mutations in three different genes, suggesting hoe-1 may be generally required for germline proliferation. We also found that reduction of hoe-1 by RNAi suppresses the multivulva (Muv) phenotype resulting from activating mutations in ras and that this suppression is likely to be indirect. This is the first demonstration of a biological role for this class of proteins in a complex eukaryote and adds important information when considering the role of ELAC2 in prostate cancer.