Here we analyzed a tissue microarray consisting of normal prostate, benign prostatic hyperplasia, high grade prostatic intraepithelial neoplasia and primary prostate cancer cases for UXT protein expression.
Loss of UXT expression in primary prostate cancer is positively associated with high Gleason grade and poor relapse-free survival.
UXT depletion in prostate cancer cells also increased retroelements expression, including LINE-1 and Alu.
"The androgen receptor pathway plays a vital role in prostate cancer growth."
However, prostate cancer patients receiving androgen deprivation therapy often relapse and develop castration-resistant prostate cancer, which still relies on the AR pathway for growth.
Our previous work identified UXT as a transcription factor that directly binds to the AR N-terminus and modulates AR transcriptional activity in prostate cancer cells.
Depletion of UXT activates DNA damage checkpoint genes, promotes proliferation, and induces cell resistance to anti-androgen treatment in prostate cancer cells.
Depletion of UXT also decreases the protein expression of unconventional prefoldin RBP5 interactor in prostate cells; we have shown that UXT and URI affect each others stability, and in complex together, UXT/URI represses AR mediated transcription and AR occupancy on AR target genes.
We then used prostate-specific Uxt KO transgenic mice and prostate cancer cell culture models to investigate UXT function in Ca P development and progression.
"Interestingly, the prostate hyperplasia in these two types of genetically altered mice has different morphologies with papillary hyperplasia more prevalent in the Pten deletion and cribriform hyperplasia more prevalent in the Uxt deletion.
In addition, the Uxt deletion mice exhibited moderate levels of prostate secretion fluid blockage, indicating that the enlargement of prostate resulted in gland obstruction and disfiguration of the organ.
Second, the accumulation of prostate secretion fluid in the anterior prostate and inflation in these glands may be a direct result of the dorsal/ventral obstruction, leading to a further increase in prostate size.
Altogether our results suggest that loss of UXT in human prostate may promote genome instability in normal prostate epithelial cells and that loss of UXT as an early event in prostate cancer may lead to chromosomal alterations."
Full text - https://doi.org/10.18632/oncotarget.26573
Correspondence to - Susan K. Logan - [email protected]
Keywords - UXT, retroelement, prostate cancer
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