Metastatic Prostate Cancer Mechanism Identified

Studies suggest that inhibition of the EZH2 enzyme may prevent suppression of oncogene
By Rick Ansorge
HealthDay Reporter

MONDAY, Feb. 15 (HealthDay News) -- An oncogene tumor-suppressor cascade may drive metastatic prostate cancer, according to research published online Feb. 14 in Nature Medicine.

Junxia Min, Ph.D., of Brigham and Women's Hospital in Boston, and colleagues performed a protein and transcriptional pattern analysis in more than 250 human prostate tumors and found that loss of the DAB2IP gene triggered a cascade of signals that initiated tumor growth and caused metastasis. In subsequent mouse studies, they used genetic approaches to identify the upstream genes responsible for controlling DAB2IP and essential downstream signals to identify the entire genetic pathway.

The researchers found that the DAB2IP gene was silenced by the polycomb-group protein histone-lysine N-methyltransferase EZH2.

"Because EZH2 is an enzyme, it has been proposed to be a potential therapeutic target," the authors write. "Our data underscore the utility of developing EZH2 inhibitors, as such agents might suppress both Ras and NF-κB -- proteins that have proven difficult to target directly -- in prostate cancer. These findings also support the possibility that such inhibitors might affect primary tumors and metastatic lesions."

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