High-level Expression of Wild-type P53 in Melanoma Cells is Frequently Associated with Inactivity in P53 Reporter Gene Assays

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Jul 16

PMID 21760960

Citations 31

Authors

Roland Houben

Sonja Hesbacher

Corinna P Schmid

Claudia S Kauczok

Ulrike Flohr

Sebastian Haferkamp

Cornelia S L Muller

David Schrama

Jorg Wischhusen

Jurgen C Becker

Affiliations

Soon will be listed here.

Abstract

Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date.

Methodology/principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5-8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53.

Conclusions/significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.

Citing Articles

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