title: High-level expression of wild-type p53 in melanoma cells is frequently associated with inactivity in p53 reporter gene assays.
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.
  
  
  RESULTS
  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
  In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.
authors.affiliation: Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Houben
authors.forename: Sonja
authors.initials: S
authors.lastname: Hesbacher
authors.forename: Corinna P
authors.initials: CP
authors.lastname: Schmid
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Kauczok
authors.forename: Ulrike
authors.initials: U
authors.lastname: Flohr
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haferkamp
authors.forename: Cornelia S L
authors.initials: CS
authors.lastname: Müller
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D017930:Genes, Reporter / Q000235:genetics*; D005821:Genetic Techniques; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53