Abstract A50: Loss of pVHL inactivates p53 by permission of interaction between p14/ARF and progerin

Abstract

Abstract Renal cell carcinoma (RCC) is a common primary renal malignancy in adults. The typical feature is the nuclear irregularity which is a basis for grading. Moreover, resistance to chemotherapy and irradiation (IR) is also one of the characters of RCC. p53 inactivation without genetic mutation and pVHL mutation in early stage are shown in RCC. However, it is still remained the question about the mechanism of the nuclear deformation and chemotherapy resistance. Here we proposed that the effect of progerin on RCC. Progerin elevated in RCC and the elimination of progerin could ameliorate the nuclear morphology. Moreover, knockdown of progerin could recover DNA damage sensitivity and p53 activation in RCC. Loss of pVHL induces elevated progerin expression, which inhibit p14/ARF by direct interaction to suppress p53 activity. Moreover, forced enhancement of progerin is found in human leukemia sample. In this study, we provide that the novel mechanism for p53 suppression in RCC and the importance of progerin in cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A50.