Ozretić, Petar; Hanžić, Nikolina; Proust, Bastien; Sabol, Maja; Trnski, Diana; Radić, Martina; Musani, Vesna; Ciribilli, Yari; Milas, Ivan; Puljiz, Zvonimir; Bosnar Herak, Maja; Levanat, Sonja; Slade, Neda
(2019)
Expression profiles of p53/p73, NME and GLI families in metastatic melanoma tissue and cell lines.
Scientific Reports, 9
(1).
ISSN 2045-2322
Abstract
Unlike other tumours, TP53 is rarely mutated in melanoma ; however, it fails to function as a tumour suppressor. We assume that its functions might be altered through interactions with several families of proteins, including p53/p73, NME and GLI. To elucidate the potential interplay among these families we analysed the expression profiles of aforementioned genes and proteins in a panel of melanoma cell lines, metastatic melanoma specimens and healthy corresponding tissue. Using qPCR a higher level of NME1 gene expression and lower levels of Δ40p53β, ΔNp73, GLI1, GLI2 and PTCH1 were observed in tumour samples compared to healthy tissue. Protein expression of Δ133p53α, Δ160p53α and ΔNp73α isoforms, NME1 and NME2, and N′ΔGLI1, GLI1FL, GLI2ΔN isoforms was elevated in tumour tissue, whereas ∆Np73β was downregulated. The results in melanoma cell lines, in general, support these findings. In addition, we correlated expression profiles with clinical features and outcome. Higher Δ133p53β and p53α mRNA and both GLI1 mRNA and GLI3R protein expression had a negative impact on the overall survival. Shorter overall survival was also connected with lower p53β and NME1 gene expression levels. In conclusion, all examined genes may have implications in melanoma development and functional inactivity of TP53.
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