Thus, our findings show that overexpression of TRIM25 promoted prostate cancer cell proliferation and cell survival by modulating p53 nuclear export mechanism with G3BP2 interaction.
We observed that PCa cell lines that are TP53 wild-type, which includes cell lines derived from AAM (MDA-PCa-2b and RC77T), did not express detectable IL-6 mRNA.
By conducting transcriptome analysis, denaturing immunoprecipitations and immunopathology, we demonstrate that the TP53-MDM2-AR-AKT cross-talk is regulated by the deubiquitinating enzyme USP12 in prostate cancer.
Thus, we concluded that p53 is a sensor for enhanced apoptosis in response to DNA damage stress, not DNA replication stress, at least in prostate cancer.
These findings highlight an important oncogenic aspect of USP10 through its modulation of the p53-G3BP2 complex and AR signaling in prostate cancer.<b>Implications:</b> These findings elucidate the oncogenic role of USP10 in prostate cancer through an increase in G3BP2 protein that inhibits p53 activity, in addition to the promotion of AR signaling.<i></i>.
Given that loss of p53 is associated with progression of prostate cancer to CRPC and NEPC, our results show that TET, by acting as a TRAIL-sensitizing agent in prostate cancer, could serve as a potential therapeutic agent in CRPC and NEPC, for which there is no cure to date.<i></i>.
The gain of MYCN and AURKA oncogenes, along with the loss of tumor suppressor genes TP53 and RB1 are key genomic alterations associated with treatment-related neuroendocrine prostate cancer.
The method was applied to the assay of p53 in human plasma sample and normal and malignant cell line lysates such as normal cell Line from mouse C3H (L929), colon cancer cell-HCT, prostate cancer cell line PC-3, and human breast adenocarcinoma cell line-MCF7.
The most prevalent mutations among patients with PC are c.1621A>C (rs3822214) in KIT, c.38G>C (rs112445441) in KRAS and c.733G>A (rs28934575) in TP53 genes.
Alterations affecting tumor suppressors and oncogenes, such as PTEN, MYC, BRCA2, and TP53, which have been long associated with aggressive PCa, demonstrated grade-dependent frequency of alterations in localized PCas.
The developed array biochip is then utilized to parallelly analyze the O-GlcNAcylation of three oncogenic transcription factors C-Myc, NF-κB and p53 in normal prostate epithelial cell (RWPE-1) and prostate cancer cell line (PC-3).
Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach.
Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis.
The current study demonstrates that combination treatment blocks the cell cycle arrest by modulation of key regulators and promotes apoptosis via p53 dependent and independent mechanism in PCa.
It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer.