Analysis by flow cytometry revealed that RCC cell proliferation inhibitory effect of SSd was achieved by inducing apoptosis and cell cycle arrest at G0/G1 phase via up-regulation of p53.
In contrast, mutational profiles within the epithelial and sarcomatoid components of sarcomatoid RCC were shown to be identical, with TP53 being the most frequently altered gene.
The loss of <i>Tp53</i> and <i>Tsc1</i> within nestin-expressing cells in mice resulted in the development of renal cell carcinomas (RCC) with high <i>Notch1</i> and <i>Nodal</i> expression, suggesting that similar downstream mechanisms contribute to tumorigenesis as a result of p53 loss in mice and p53 polymorphism in humans.
Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53 complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62.
Mass spectrometry analysis revealed that streptonigrin binds to the N-terminus of TGase 2 (amino acids 95⁻116), which is associated with inhibition of TGase 2 activity in vitro and with p53 stabilization in RCC.
Recurrent secondary molecular alterations in clear cell RCC (BAP1, SETD2, PBRM1, and TP53) and papillary RCC (CDKN2A) may be associated with poor prognosis; however, intratumoral genomic heterogeneity may limit the clinical utility of these molecular biomarkers in renal mass biopsies.
Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53α, p53β, p53γ) in tumors were determined by RT-PCR and real-time PCR.
Among the 11 non-responders 7 (64%) were wild-type, 2 (18%) were p53 mutated and 2 (18%) VHL1 mutated.No significant associations were found among RCC histotype, mutation variants and response to therapies.
In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21<sup>Cip1/Waf1</sup>, which are mediated by increased RhoA-ROCK activities.
Spearman ranking correlation analysis showed that expression of PUMA, MCL-1, and p53 in was negatively correlated with RCC (r = -0.504, P = 0.001; r = -0.413, P = 0.008).
CAIX, p53 and Bcl-2 might play important roles in the transformation from renal cell carcinoma to high malignant sarcomatoid differentiation, and these three immunohistochemical markers are adverse prognostic factors for the survival of patients with RCC with sarcomatoid differentiation.
We found that TGase 2 competes with human double minute 2 homolog (HDM2) for binding to p53; promotes autophagy-dependent p53 degradation in renal cell carcinoma (RCC) cell lines under starvation; and binds to p53 and p62 simultaneously without ubiquitin-dependent recognition of p62.
Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived.Using laser-microdissection of p53-expressing tumor cells, we identified TP53-mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient.