Smith Marsha M, Levitan Diane J
Department of Functional Genomics/Discovery Technologies, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Dev Biol. 2004 Feb 1;266(1):151-60. doi: 10.1016/j.ydbio.2003.10.016.
The potential prostate cancer susceptibility gene ELAC2 has a Caenorhabditis elegans homolog (which we call hoe-1, for homolog of ELAC2). 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.
潜在的前列腺癌易感基因ELAC2有一个秀丽隐杆线虫同源基因（我们将其称为hoe-1，即ELAC2的同源基因）。我们利用RNA干扰降低该基因的活性，探究了此基因的生物学作用。我们发现，遭受hoe-1 RNA干扰的线虫生长缓慢且不育。不育是由于生殖系增殖急剧减少以及生殖系细胞核的细胞周期停滞所致。我们发现，hoe-1是三种不同基因突变所呈现的过度增殖表型所必需的，这表明hoe-1可能是生殖系增殖普遍所需的。我们还发现，通过RNA干扰降低hoe-1可抑制由ras激活突变导致的多外阴（Muv）表型，且这种抑制可能是间接的。这是此类蛋白质在复杂真核生物中的生物学作用的首次证明，在考虑ELAC2在前列腺癌中的作用时增添了重要信息。
