IDENTIFICATION OF NEW GENES SHOWS A COMPLEX PATH TO CANCER

UMass Medical School investigators define multi-step pathway that allows for cancer cell development and growth

October 25, 2007

WORCESTER, Mass. —The conversion of a normal cell to a cancer cell cannot be defined by just one mutation. Rather, the process includes a number of steps that often include the activation of oncogenes believed to lead to cancer and the related inactivation of genes that suppress tumor growth and promote cancer cell death. This inactivation, or epigenetic silencing, of tumor suppressor genes often leads to rapid cancer cell growth and is therefore an intriguing pathway for scientists to investigate. Now, researchers at the University of Massachusetts Medical School have identified a network of genes in a particular silencing pathway, enhancing the understanding of how oncogenes direct the silencing of tumor suppression and suggesting an alternate strategy for the development of cancer therapeutics.

In “An elaborate pathway required for Ras-mediated epigenetic silencing,” published in the October 24 issue of Nature, Howard Hughes Medical Institute Investigator Michael R. Green, MD, PhD, the Lambi and Sarah Adams Chair in Genetic Research and professor of molecular medicine and biochemistry & molecular pharmacology, and colleagues at UMMS employed RNA interference technology to identify 28 genes in the pathway by which a particular oncogene (Ras) directs the epigenetic silencing of a tumor suppressor gene (Fas). While these genes, dubbed “Ras epigenetic silencing factors,” comprised a number of different functions in the cell, they all contributed to the common pathway that suppressed Fas expression and allowed for increased cancer cell growth.

Although a current class of anti-cancer agents known as histone deacetylase (HDAC) inhibitors have proven to be beneficial by broadly and interfering with epigenetic silencing, Green and collaborators believe that by better understanding this sophisticated network that facilitates the development and growth of cancer cells, more efficacious drugs that selectively inhibit the epigenetic silencing pathway can be developed. Subsequently, by identifying the individual components of the Ras pathway that are required for silencing and contribute to the conversion of normal cells to cancerous cells, Green and colleagues have provided a range of promising targets for new drug development.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research.  The Medical School attracts more than $176 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine, hailed as the "Breakthrough of the Year" in 2002 by Science magazine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu