University of Massachusetts Medical School researchers say that they have identified 28 genes required for the activation of a cancer promoting pathway.
The investigators performed a genome-wide RNAi screen in K-ras-transformed NIH 3T3 cells. They discovered these genes, which they believe are necessary for ras-mediated epigenetic silencing of the Fas, a proapoptotic gene silenced in certain cancers.
They also report finding that at least nine of the 28 genes including the DNA methyltransferase DNMT1 are associated with specific regions of the Fas promoter in transformed cells but not in untransformed cells. Silencing any of these genes prevented DNMT1 from binding to the Fas promoter region and initiating hypermethylation, which resulted in restoration of Fas expression, the scientists note.
Of the 28 genes involved in the pathway, nine of them are required for anchorage-independent growth and tumorigenicity of K-ras-transformed cells, according to the team.
The study was published in the October 25 issue of Nature.