Meanwhile exon 8 mutation of p53 gene was detected in the renal tumor by microdissection-PCR-SSCP and sequencing technique indicating that p53 gene mutation may play an important role in malignant transformation.
Inactivation of the TCA cycle enzyme, fumarate hydratase (FH), drives a metabolic shift to aerobic glycolysis in FH-deficient kidney tumors and cell lines from patients with hereditary leiomyomatosis renal cell cancer (HLRCC), resulting in decreased levels of AMP-activated kinase (AMPK) and p53 tumor suppressor, and activation of the anabolic factors, acetyl-CoA carboxylase and ribosomal protein S6.
The potential functional interactions between WT1 and p53 in control of IGF-IR promoter activity were addressed by transient coexpression of vectors encoding different isoforms of WT1, together with IGF-IR promoter-luciferase reporter constructs, in p53-null osteosarcoma-derived Saos-2 cells, wild-type p53-expressing kidney tumor-derived G401 cells, and mutant p53-expressing, rhabdomyosarcoma-derived RD cells.
Infrequent p53 gene mutations and lack of p53 protein expression in clear cell sarcoma of the kidney: immunohistochemical study and mutation analysis of p53 in renal tumors of unfavorable prognosis.
Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF.
While this study is unable to clarify the relative prevalence and importance of p53 mutational events in the pathogenesis of this aggressive renal tumor of childhood, it is reasonably suggestive that alterations in the p53 tumor suppressor gene do occur in CCSK.