Inositol polyphosphate 4-phosphatase type II regulation of androgen receptor activity.

ABSTRACT: Activation and transcriptional reprogramming of AR in advanced prostate cancer frequently coincides with the loss of two tumor suppressors, INPP4B and PTEN, which are highly expressed in human and mouse prostate epithelium. While regulation of AR signaling by PTEN has been described by multiple groups, it is not known whether the loss of INPP4B affects AR activity. Using prostate cancer cell lines, we showed that INPP4B regulates AR transcriptional activity and the oncogenic signaling pathways Akt and PKC. Analysis of gene expression in prostate cancer patient cohorts showed a positive correlation between INPP4B expression and both AR mRNA levels and AR transcriptional output. Using an Inpp4b^-/- mouse model, we demonstrated that INPP4B suppresses Akt and PKC signaling pathways a

SUBMITTER: Zhang M 

PROVIDER: S-EPMC6377303 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature