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IU research reveals link between molecular mechanisms in prostate cancer and Ewing's sarcoma

Nov. 2, 2016

Medical researchers at Indiana University Bloomington have found evidence for a link between prostate cancer, which affects millions of men age 50 and older, and Ewing's sarcoma, a rare form of cancer that affects children and young adults.

Tumor tissue illustration

These slides show tumor tissue where ERG and EWS genes interact normally, top, and tumor tissue where ERG has been modified to prevent interaction with EWS, bottom. The green sections indicate cellular proliferation, showing that tumors grow faster when ERG-EWS remains uninhibited. | PHOTO BY INDIANA UNIVERSITY

The results of the study, reported today in the journal Cell Reports, suggest that the molecular mechanism that triggers the rare disease Ewing's sarcoma could act as a potential new direction for the treatment of more than half of patients with prostate cancer.

A form of bone and soft tissue cancer that affects about one in 1 million children and young adults age 10 to 19, Ewing's sarcoma is terminal in 44 percent of teens age 15 to 19 and 30 percent of children. Over 100,000 men are diagnosed with prostate cancer each year in the U.S, with more than 99 percent of cases occurring after age 50.

"This research shows that the molecular mechanism involved in the development of most prostate cancers is very similar to the molecular mechanism known to cause Ewing's sarcoma," said Peter Hollenhorst, an associate professor in the Medical Sciences Program at IU Bloomington, a part of the IU School of Medicine. "It also suggests that this mechanism might be used to explore a common treatment for both diseases, one of which is not often pursued by drug companies due to its rarity."

Hollenhorst is also a member of the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis.

Other authors on the paper include Vivekananda Kedage, a graduate student in the IU Bloomington College of Arts and Sciences' Department of Molecular and Cellular Biochemistry, and Travis J. Jerde, an associate professor in the Department of Pharmacology and Toxicology at the IU School of Medicine in Indianapolis. Kedage is the first author on the study.

Peter Hollenhorst


There are 28 genes in the human body known as ETS genes, four of which are known to produce proteins that cause prostate cancer. These four cancer-causing genes, or "oncogenes," are called ETV1, ETV4, ETV5 and ERG, the last of which has been implicated in over 50 percent of all prostate cancers. The other three combined play a role in about 7 percent of prostate cancers.

Hollenhorst's study is the first to show that the proteins produced by the EWS gene interact with all four ETS proteins known to trigger prostate cancer. Moreover, the EWS protein only interacts with proteins from these four harmful ETS genes, not the other 24 ETS genes not found to play a role in prostate cancer.

"A molecular mechanism that sets these four genes apart from the ones that don’t trigger cancer has never been identified until now," Hollenhorst said. "This is significant because it suggests that any compound that disrupts EWS-ETS interaction would specifically inhibit the function of the four oncogenes and not the others, which play important roles in the healthy function of the body."

Based upon the strength of the work reported in the study, Hollenhorst and colleagues at IU Bloomington and the IU School of Medicine have received a grant from the IU Simon Cancer Center to search for molecules that could potentially disrupt ETS-EWS interaction. Their work will be conducted in collaboration with a facility at Purdue University that specializes in screening for these molecules.

The researchers' work on the Bloomington campus aligns with priorities outlined in the university’s Bicentennial Strategic Plan, including catalyzing research and improving the state and nation's health.

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