High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays

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 clarif...

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Published in:	PloS one Vol. 6; no. 7; p. e22096
Main Authors:	Houben, Roland, Hesbacher, Sonja, Schmid, Corinna P, Kauczok, Claudia S, Flohr, Ulrike, Haferkamp, Sebastian, Müller, Cornelia S L, Schrama, David, Wischhusen, Jörg, Becker, Jürgen C
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 08-07-2011 Public Library of Science (PLoS)
Subjects:	Analysis Apoptosis Base Sequence Biology Biotechnology Cancer Cell adhesion & migration Cell Cycle Cell Line, Tumor Cytotoxicity Deactivation Deoxyribonucleic acid Dermatology DNA DNA Mutational Analysis Exons Gene expression Genes Genes, Reporter - genetics Genetic aspects Genetic research Genetic Techniques Humans Immunoglobulins Inactivation Kinases Melanoma Melanoma - metabolism Melanoma - pathology Metastasis Molecular Sequence Data Mutation Mutation - genetics p53 Protein Proteins Reporter gene Rodents Senescence Sequences Skin Neoplasms - metabolism Skin Neoplasms - pathology Transcription Tumor necrosis factor-TNF Tumor proteins Tumor suppressor genes Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors
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Summary:	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. 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. In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: RH JW JCB. Performed the experiments: RH S. Haferkamp CPS UF CSK CSLM S. Hesbacher. Analyzed the data: RH CSLM CSK JCB. Contributed reagents/materials/analysis tools: JCB. Wrote the paper: RH DS JW JCB.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0022096