RCC in transplants shared several clinicopathological features with those in dialysis patients, which included small size and multiplicity of tumor, relatively high frequency of presence of ACDK, and papillary type of RCC. p53 gene mutations were infrequent in RCC of any clinical setting.
These findings suggest that, in RCC, inactivation of p53 might contribute to progression of the disease but inactivation of p21WAF1 and bax are not likely to play significant roles in the defective p53 pathway.
These data suggest that: (a) mutation of p53 contributes to the overexpression of IL-6 in RCC; and (b) wt p53 represses IL-6 expression, at least in part, by interfering with specific transcription factor binding to the IL-6 promoter.
To investigate the role of these biomarkers in renal cancer, we analyzed the immunohistochemical distribution of CD44's expression on formalin fixed paraffin embedded tissue from 67 renal cell carcinomas and correlated with clinicopathologic parameters as well as with p53 suppressor gene expression.
Taken together, our findings support a role for pVHL in elevating p53 expression, implicate HuR in enhancing VHL-mediated p53 translation, and suggest that VHL-mediated p53 upregulation may contribute to pVHL's tumor suppressive functions in renal cell carcinoma.
Remarkably, cells of normal kidney epithelium also caused partial p53 repression in cell fusion experiments, suggesting that RCC-specific p53 repression may be based on an unknown dominant mechanism also acting in normal kidney tissue.
Destruction of HIF-1alpha by p53 was corroborated in the present study by using pVHL-deficient RCC4 (renal carcinoma) cells, supporting the notion of a pVHL-independent degradation process.
In contrast to agents that target IkappaB kinase 2, 9AA and quinacrine can effectively suppress both basal and inducible activities of NF-kappaB, representing inhibitors of a previously undescribed type that convert NF-kappaB from a transactivator into a transrepressor, leading to accumulation of inactive nuclear complexes with unphosphorylated Ser-536 in the p65/RelA subunit. p53 function in RCC can be restored by ectopic expression of a superrepressor of IkappaB as effectively as by 9AA-derived compounds.
To investigate the prognostic value of DNA ploidy, Ki-67 index and p53 expression in relation to disease-related survival in a consecutive series of patients with renal cell carcinoma (RCC).
These results indicate that the deletion in the INK4a/ARF locus might contribute to tumor progression in RCC at least partly by functional inactivation of wild-type p53.