Expression of p53 in renal carcinoma cells is independent of pVHL.
Renal clear-cell carcinoma (RCC) is the predominant form of kidney cancer and is highly refractory to conventional anti-cancer therapies. The status of p53 tumor suppressor gene has been correlated with the efficacy of radio- and chemotherapies, where presence of mutant p53 is associated with reduced responsiveness to treatment. However, p53 itself is rarely mutated in RCC, rather suggesting that the p53 pathway might be compromized in RCC cells. In support of this notion, the transactivation property of normal p53 was shown to be repressed in various transformed kidney epithelial cells via an unknown dominant-negative mechanism. Mutation of the von Hippel-Lindau (VHL) gene causes familial VHL disease, which includes predisposition to RCC. Moreover, biallelic inactivation of VHL has been observed in the vast majority of sporadic RCC. Recently, the expression of pVHL in RCC cells was demonstrated to elevate the expression of p53 by inducing the binding of RNA-stabilizing protein HuR to the 3'untranslated region of p53 mRNA. Contrary to this finding, we report here that the reconstitution of a variety of VHL(-/-) RCC lines including 786-O, RCC4, and A498 or non-RCC cells with wild-type pVHL does not influence the expression of p53 and fails to induce p53-responsive gene p21CIP1/WAF1 or p53-responsive reporters. These results suggest that the expression of p53 in RCC cells is independent of pVHL.
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ont., Canada M5S 1A8.
Natalie H
NH
Stickle
Lynn S
LS
Cheng
Ian R
IR
Watson
Noa
N
Alon
David
D
Malkin
Meredith S
MS
Irwin
Michael
M
Ohh
D000595:Amino Acid Sequence; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53