Dartmouth Research Helps Explain Protein Function in Tumor Cell Growth
June 21, 2010
New research from Dartmouth-Hitchcock Norris Cotton Cancer Center helps explain why the Myc protein, found in the nucleus of cells and crucial to the function of cell division, sometimes reaches elevated levels that cause it to be an agent in the growth of cancerous tumors.
Published this month in the peer-review journal Genes & Development, the paper, titled "Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells" and authored by Cancer Center researchers Seung H. Choi, PhD, Jason B. Wright, Scott A. Gerber, PhD, and Michael D. Cole, PhD, identifies a novel protein complex, E3 ligase, that in normal cells regulates the degradation of Myc protein. In tumor cells, however, this degradation is significantly dampened.
The team's data suggest that inactivation of the Myc-degradation pathway can be a preliminary step in cancer development. In tumor cells, Myc becomes a kind of super-growth promoter. "We want to know exactly what's defective in tumor cells, and we keep coming back to the Myc protein," explains Dr. Cole. "The more Myc you have, the more cell growth you have. For some reason, in cancer cells the regulation of Myc is disrupted and tumor cells grow like the accelerator is on the floor all the time."
Dr. Cole's team found that in normal cells, the E3 ligase rids the cell of Myc after about 20 minutes (its half-life). In tumor cells, the function of this E3 ligase becomes inactive, extending Myc's half-life to 40 and even 60 minutes.
"Understanding Myc is fundamental to understanding cancer cells," comments Dr. Cole, who has studied Myc for 28 years. "In this paper we are able to show cause and effect for Myc degradation. What we still need to understand is why, in tumor cells, the degradation machinery for Myc is turned off."
Dartmouth-Hitchcock Norris Cotton Cancer Center combines advanced cancer research at Dartmouth Medical School with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center, at Dartmouth-Hitchcock regional locations in Manchester and Keene, NH, and St. Johnsbury, VT, and at 11 partner hospitals throughout New Hampshire and Vermont. It is one of 40 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation.