Study of placenta unexpectedly leads to cancer gene

December 16, 2008

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. Next, researchers set out to find SENP2 target proteins that could be involved in arresting cell growth.

In the journey, 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 tumor suppressor. When p53 is functioning normally, it acts as a crucial guardian of the genome, or a checkpoint, by fixing genetic mistakes as they arise.

But 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.

Researchers also found that SENP2 indirectly regulates p53 activity through another protein called Mdm2, which was already known to be involved in some cancers. In cells lacking SENP2, the Mdm2 becomes trapped in the nucleus, and is unable to halt p53, allowing it to accumulate within the cell. This disruption leads to distinct problems in cell cycle progression and normal gene replication.
-end-
The National Cancer Institute funded the research.

University of Rochester Medical Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.