Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance.
Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer.
The requirement for PKN activity in prostate cancer initiated by loss of phosphatase and tensin homolog deleted on chromosome 10 (Pten), and the potential redundancy between PKN isoforms, was analyzed by prostate-specific deletion of Pkn1, Pkn2, and Pten.
Our study therefore reveals a functional circuit linking PTEN and LXR, and highlights LXRs as metabolic gatekeepers that are able to constrain PCa progression.Treatment of prostate cancer, especially in its advanced stage, is still challenging; therefore, strategies to prevent metastatic dissemination are of great interest.
The overexpression of ERG and the inactivation of PTEN have been shown to be important drivers of carcinogenesis in large series of prostate cancer, but the genetics of transition zone tumors have not been well characterized.
Genomic aberrations of the PI3K-AKT axis, in particular affecting PTEN, are common in PCa, and compounds targeting different kinases in this pathway are showing promise in clinical trials.
To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p).
Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice).
ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain).
Compared to high grade conventional PCa matched for the pathological stage, cell proliferation was higher (P = 0.04) in DAC, and complete PTEN loss more frequent (P = 0.023).
Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa.
PTEN deletion increased PI(3,4)P<sub>2</sub> levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P<sub>2</sub> levels across several EGF-stimulated prostate and breast cancer lines.