Abstract
BackgroundInactivation 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 FindingsImmunohistochemical 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/SignificanceIn melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.
Highlights
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
Immunohistochemical analysis of 185 melanoma samples demonstrated that in the majority of tumors high levels of p53 are expressed in a considerable proportion of the tumor cells (Figure 1 A and B)
Absence of p53 mutation in melanoma p53 mutation frequencies of 21, 24 or 29% have been described for melanoma tissues and short term melanoma cell cultures [17,18,19]
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. In melanoma cell lines which have preserved the p53 wild-type geno/phenotype observed in situ, we demonstrate transcriptional inactivity of the protein in 6 out of 10 cell lines suggesting active silencing as the mode of p53 inactivation in melanoma. Immunohistochemical analysis of 185 melanoma samples demonstrated that in the majority of tumors high levels of p53 are expressed in a considerable proportion of the tumor cells (Figure 1 A and B).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
