Several genes that hold promise as potential targets for new drugs against cancer have been discovered by researchers from the University of Wyoming using experiments involving worms.
Corresponding author David S. Fay, Ph.D., and graduate student Stanley R.G. Polley employed a strain of nematode Caenorhabditis elegans worms carrying a gene mutation similar to one inactivated in many human cancers. This gene—called “LIN-35” in the C. elegans worms and “pRb” in humans—is believed to control at least several aspects of cancer tumor progression, including cell growth and survival.
Researchers systematically inactivated other individual genes in the genome of the mutant LIN-35 worm, using a genome-wide RNA-interference-feeding screen for suppressors of the gene. Of 26 suppressors identified, 17 fell into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators.
As they deactivated various genes, scientists identified those leading to a reversal of defects caused by the loss of LIN-35, suggesting that they could be used as targets for anticancer therapies.
Researchers also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes.
“Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene,” according to the study.
Dr. Fay and Polley published their results in “A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans,” published in the August issue of the journal Genetics. The paper holds the distinction of being the first one published by that journal to be accompanied by a primer.
The Genetics study is available at http://www.genetics.org/content/early/2012/04/25/genetics.112.140152.full.pdf+html