Identification of new genes shows a complex path to cancer: UMass Medical School investigators define multi-step pathway thatallows for cancer cell development and growth

Abstract

The conversion of a normal cell to a cancer cellcannot be defined by just one mutation. Rather, the process includesa number of steps that often include the activation of oncogenesbelieved to lead to cancer and the related inactivation of genes thatsuppress tumor growth and promote cancer cell death. Thisinactivation, or epigenetic silencing, of tumor suppressor genesoften leads to rapid cancer cell growth and is therefore anintriguing pathway for scientists to investigate. Now, researchers atthe University of Massachusetts Medical School have identified anetwork of genes in a particular silencing pathway, enhancing theunderstanding of how oncogenes direct the silencing of tumorsuppression and suggesting an alternate strategy for the developmentof cancer therapeutics.In "An elaborate pathway required for Ras-mediated epigeneticsilencing," published in the October 24, 2007 issue of Nature, HowardHughes Medical Institute Investigator Michael R. Green, MD, PhD, theLambi and Sarah Adams Chair in Genetic Research and professor ofmolecular medicine and biochemistry & molecular pharmacology, andcolleagues at UMMS employed RNA interference technology to identify28 genes in the pathway by which a particular oncogene (Ras) directsthe epigenetic silencing of a tumor suppressor gene (Fas). Whilethese genes, dubbed "Ras epigenetic silencing factors," comprised anumber of different functions in the cell, they all contributed tothe common pathway that suppressed Fas expression and allowed forincreased cancer cell growth.Although a current class of anti-cancer agents known as histonedeacetylase (HDAC) inhibitors have proven to be beneficial by broadlyand interfering with epigenetic silencing, Green and collaboratorsbelieve that by better understanding this sophisticated network thatfacilitates the development and growth of cancer cells, moreefficacious drugs that selectively inhibit the epigenetic silencingpathway can be developed. Subsequently, by identifying the individualcomponents of the Ras pathway that are required for silencing andcontribute to the conversion of normal cells to cancerous cells,Green and colleagues have provided a range of promising targets fornew drug development.About the University of Massachusetts Medical School:The University of Massachusetts Medical School, one of the fastestgrowing academic health centers in the country, has built areputation as a world-class research institution, consistentlyproducing noteworthy advances in clinical and basic research. TheMedical School attracts more than $176 million in research fundingannually, 80 percent of which comes from federal funding sources. Thework of UMMS researcher Craig Mello, PhD, an investigator of theprestigious Howard Hughes Medical Institute (HHMI), and his colleagueAndrew Fire, PhD, then of the Carnegie Institution of Washington,toward the discovery of RNA interference was awarded the 2006 NobelPrize in Physiology or Medicine, hailed as the "Breakthrough of theYear" in 2002 by Science magazine and has spawned a new and promisingfield of research, the global impact of which may prove astounding.UMMS is the academic partner of UMass Memorial Health Care, thelargest health care provider in Central Massachusetts. For moreinformation, visit www.umassmed.edu--