Nat commun: potential therapeutic target of PTEN mutation prostate cancer

October 26, 2019 / Biovalley BIOON / -- PTEN is a tumor suppressor gene, which mutates in about 20% of primary prostate cancer and up to 50% of castrated resistant prostate cancer PTEN relies on another gene, arid4b The findings were published in nature communications by researchers at the George Washington University (GW) cancer center This finding provides a potential therapeutic target for prostate cancer with common PTEN mutations Photo source: nature communications "the loss of tumor suppressor PTEN due to mutation or deletion is not only common in human prostate cancer, but also plays an important role in other cancers "We want to find out more about PTEN and other genes it may depend on to provide new treatment options for patients with PTEN mutations," said Wu ray Chang, associate professor of Biochemistry and molecular medicine at GW School of medicine and health sciences "We found that PTEN has an important relationship with arid4b gene, which provides a new therapeutic target for treatment "Wu and his coauthor, Dr Mei Yi Wu (Associate Professor of medicine, GW School of medicine and Health Sciences), and other members of the research team found interesting evidence from data from several prostate cancer cohorts: cancers with PTEN mutations almost always retain arid4b One of the functions of arid4b gene is to recombine chromatin to form chromosome This "mutually exclusive" pattern between PTEN and arid4b provides the team with the first clue about its potential importance in prostate cancer It was further found that the inhibition of arid4b expression in PTEN mutant cancer cells significantly inhibited the growth of cancer cells and increased cell death In contrast, when cancer cells containing functional PTEN were used, the observed effect was less significant, indicating that prostate cancer with PTEN deficiency was dependent on arid4b Importantly, the team was able to validate these findings using a prostate cancer mouse model that knocks out PTEN As expected, the absence of PTEN alone in mice can lead to prostate cancer In contrast, mice lacking PTEN and arid4b at the same time did not develop tumors In general, these results led the team to conclude that PTEN function depends on the presence of arid4b, and in the case of PTEN gene deletion, arid4b was identified as a potential therapeutic target for prostate cancer However, more research is needed to develop a method for arid4b Reference materials: Ray Chang Wu et al, identification of the pten-arid4b-pi3k pathway reeveals the dependency on arid4b by PTEN deficient prostate cancer, nature communications (2019) Doi: 10.1038/s41467-019-12184-8