Naslov
Functional interplay between p53 and p53/p73, NME and GLI protein families in human melanoma

Autori
Hanžić, Nikolina ; Proust, Bastien Lucien Jean ; Ozretić, Petar ; Radić, Martina ; Horvat, Anđela ; Milas, Ivan ; Puljiz, Zvonimir ; Herak Bosnar, Maja ; Levanat, Sonja ; Slade, Neda

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Translating Science of Medicine - Targets and Therapeutics, Fifth Meeting of the Croatian Association for Cancer Research with International Participation : Poster presentations, in Libri oncologici, Vol. 46 No. Supplement 1 / Ozretić, Petar ; Levanat, Sonja - Zagreb : Klinički bolnički centar Sestre milosrdnice, 2018, 51-51

Skup
5th Meeting of the Croatian Association for Cancer Research with International Participation: Translating Science to Medicine "Targets and Therapeutics" (HDIR-5)

Mjesto i datum
Zagreb, Hrvatska, 08.11.2018. - 10.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
p53 ; p73 ; NME ; GLI ; melanoma

Sažetak
In metastatic melanoma tumor suppressor protein p53 is not functional, although it is rarely mutated (less than 10%). Despite the low rate of mutations, p53 fails to function as tumor suppressor and tumor cells continue to proliferate and spread. Therefore, the question arises what in the metastatic melanoma prevents the wild type p53 protein to function. Since p53 interactions play a significant role in tumorigenesis, we have investigated whether the p53 protein function can be altered by interactions with p53 low molecular weight isoforms, p73 isoforms, and NME and GLI families of proteins. Therefore, we studied the protein expression profile of p53 and its potential interaction partners (p73/NME/GLI) in metastatic melanoma and in adjacent healthy skin tissue. In the study on 38 patients with metastatic melanoma, the expression of p53, p73, NME and GLI protein families was determined by western blot analysis. Protein expression analysis showed elevated expression of Δ133p53α, Δ160p53α, ΔNp73α, NME1, NME2, GLI1_160 kDa, GLI1_130 kDa and GLI2_133 kDa in tumor samples compared with healthy tissue samples. Strong correlations were detected only between TAp73β and p53α, and GLI3R and p53α. The remaining correlations were mostly moderate (p53α with Δ160p53α, TAp73α, ΔNp73α, GLI1_118 and GLI1_160). Interestingly, Δ133p53β was negatively correlated with p53α. We have shown that p53 forms complexes with p53 and p73 isoforms hence inhibiting its transcriptional and apoptotic activity. Although NME and GLI did not form complexes with p53, they were able to modify its activity. Defining the interactions between protein p53 and other proteins could contribute to better understanding of the molecular basis of melanoma and finally lead to the development of new approaches in melanoma treatment.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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