The DU145 cell line harbors a TS mutant of p53 and, in addition to being a widely used model of human prostate carcinoma, may also reveal new insights into p53 function due to the unique transcriptional properties of its TS phenotype.
The findings of the current study suggest that assessment of biologic changes (including p53 alterations in regional lymph node metastases) could be of value in the assessment of the biologic aggressiveness of prostate carcinoma, whereas p53 expression in the primary tumor does not appear to influence patient outcome.
Doc induced prostate cancer cell apoptosis at high levels in p53-null PC3 cells, at intermediate levels in p53-mutant DU145 cells and at low levels in p53 wild-type LNCaP cells.
The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.
These observations in clinical specimens of primary and metastatic sites provide evidence for the association of the p53 gene in the progression of human prostate carcinoma.
Furthermore, these findings suggest that a significant component of the p53 G(1) arrest pathway might be inactivated in prostate cancer even in the absence of genetic mutations in p53.
Our data, therefore, suggest that enzalutamide's high efficacy is at least partially independent of AR and p53 protein expression, which are frequently lost in advanced PC.
Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene.
Interferon-gamma and its functional receptors overexpression in benign prostatic hyperplasia and prostatic carcinoma: parallelism with c-myc and p53 expression.
Downregulation of the proapoptotic p53 target gene glioma pathogenesis-related protein 1 (GLIPR1) occurs frequently in prostate cancer, but the functional meaning of this event is obscure.
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.
Decreased PTEN expression did not reduce RAD51 expression or clonogenic survival following PARPi among prostate cancer cells that vary in TP53 and PTEN.
Whereas TP53 mutations typical of prostate cancer were found at a frequency consistent with the literature, no KLF6 mutations were found in any of the tumour samples nor in the three prostate cancer cell lines.
Seventy-five patients with advanced prostate cancer (clinical stage C: 11, stage D1: 8, stage D2: 56), who all underwent androgen ablation, had tissue specimens obtained prior to hormonal therapy and studied immunohistochemicaly for p53 (Mab D07) and p21 (Mab EA10) expression.
Also MDM2, a negative p53 regulator that interacts with retinoblastoma (Rb), E2F, p19(arf) and the ras-mitogen-activated protein kinase(MAPK) cascade plays an important role in prostate cancer progression and prognosis.
Prospective studies are urgently needed to confirm the independent prognostic value of decreased p27Kip1 protein expression together with overexpression of the p53 tumour suppressor protein in patients with localized prostate cancer.
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.