University of Rochester Medical Center scientists discovered a gene mutation that impairs the placenta and also is influential in cancer development, according to a study published online December 16, 2008, in the journal PLoS (Public Library of Science) Biology.
The investigation is the first to link the key placental gene, SENP2, to the well-known p53 protein, which is defective in 50 percent of all cancers.
Until now, the SENP2 gene's role in early embryo development was not known. As a result of making the connection between SENP2 and the potent cancer stimuli, it will be possible to gain more insight into the complex genetic network involved in cancer, and to develop new therapies, said lead author Wei Hsu, Ph.D., associate professor of Biomedical Genetics and Oncology, of the James P. Wilmot Cancer Center.
Hsu and former graduate student Shang-Yi Chiu, currently a postdoctoral fellow at Howard Hughes Medical Institute, Dana-Farber Cancer Institute at Harvard University, have been investigating how cellular signaling triggered by gene mutations affect embryo development in mice. The goal is to better understand the genetic causes and possible treatments for a number of diseases.
"What we discovered was an unexpected interaction between an old player, p53, and a new player, SENP2," said Hsu, who also has an appointment in the URMC Center for Oral Biology.
SENP2 (SUMO-specific protease 2) is highly expressed in trophoblast cells, which are the stem cells required to form the placenta. The placenta surrounds, protects and nourishes the developing fetus. While investigating disruption of placental formation in a mouse model, Hsu's team observed that embryos lacking SENP2 failed to properly make placental tissue.
The failure occurred, researchers discovered, because the cells that give rise to the placental tissues had undergone cell cycle arrest, and were trapped in a state of suspended growth. Nex
|Contact: Leslie Orr|
University of Rochester Medical Center