Gene mutation in placenta linked to cancer development

December 17th, 2008 - 2:11 pm ICT by ANI  

Washington, Dec 17 (ANI): While studying placenta, scientists from University of Rochester Medical Centre have come across a genetic mutation that impairs the organ and is also influential in cancer development.

The researchers have discovered a link between the key placental gene, SENP2 and well-known p53 protein, which is defective in 50 percent of all cancers.

The protein p53 performs a vital job of tumour suppression. It acts as a crucial guardian of the genome, or a checkpoint, by fixing genetic mistakes as they arise.

“What we discovered was an unexpected interaction between an old player, p53, and a new player, SENP2,” said lead author Wei Hsu, Ph.D., associate professor of Biomedical Genetics and Oncology, of the James P. Wilmot Cancer Centre.

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 because the cells that give rise to the placental tissues had undergone cell cycle arrest, and were trapped in a state of suspended growth.

In the further study, researchers set out to find SENP2 target proteins that could be involved in arresting cell growth.

They discovered that p53 or proteins that modify p53 activity were harmed by the SENP2 deficiency. The consequence was that p53 could no longer perform its vital job as a tumour suppressor.

When the p53 molecule is aberrantly regulated, either by an outside virus or an inherited genetic abnormality, the risk of cancer is higher because p53 cannot perform its job.

The researchers also found that SENP2 indirectly regulates p53 activity through another protein called Mdm2, which was already known to be involved in some cancers.

The study is in the journal PLoS (Public Library of Science) Biology. (ANI)

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