Naslov
Diversed Expression of Short p53 Family Isoforms May Affect Melanoma Aggressiveness

Autori
Tadijan, Ana ; Precazzini, Francesca ; Hanžić, Nikolina ; Radić, Martina ; Gavioli, Nicolò ; Vlašić, Ignacija ; Ozretić, Petar ; Pinto, Lia ; Škreblin, Lidija ; Barban, Giulia ; Slade, Neda ; Ciribilli, Yari

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

Izvornik
“HDIR-6: Targeting Cancer” The 6th Meeting of the Croatian Association for Cancer Research with International Participation : Book of Abstracts / Ozretić, Petar - Zagreb : Hrvatsko društvo za istraživanje raka (HDIR), 2022, 50-50

ISBN
978-953-48672-1-1

Skup
6th Meeting of the Croatian Association for Cancer Research with International Participation: Targeting Cancer (HDIR-6)

Mjesto i datum
Zagreb, Hrvatska, 10.11.2022. - 12.11.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
melanoma ; p53 family isoforms ; p73 family isoforms ; vemurafenib ; resistance

Sažetak
Metastatic melanoma is the most aggressive form of skin cancer. Despite currently available therapy targeting BRAF and MEK kinases, as well as immunotherapy, the treatment of melanoma remains a challenge due to resistance to therapy. Thus, it is of utmost importance to investigate the molecular pathways crucial for melanoma development and therapy resistance. The TP53 gene, the guardian of the genome, is altered in more than 50% of human cancers but is rarely mutated in melanoma. Shorter p53 family isoforms, whose significance has just recently become evident, can act as modifiers of the p53- dependent responses including its tumor suppressive function. We have analyzed the gene and protein expression of p53 and p73 isoforms in a panel of human melanoma cell lines with different TP53 and BRAF status, in normal conditions and after the treatment with common DNA-damaging agents or targeted therapy. We generated stable clones of H1299 p53 null cells expressing the less characterized short isoforms Δ160p53α, Δ160p53β, and Δ160p53γ. Furthermore, we developed two human melanoma cell lines resistant to the BRAF inhibitor vemurafenib and examined the change in the expression of the p53 family isoforms after acquisition of resistance. Our results show that human melanoma cell lines express a wide array of p53 and p73 isoforms. We demonstrated for the first time that Δ160p53α, and to a lesser extent Δ160p53β, can be recruited on chromatin, and that Δ160p53γ can localize in perinuclear foci. Importantly, H1299 cells stably expressing Δ160p53 isoforms demonstrated higher proliferation and in vitro migration. Finally, melanoma cells resistant to vemurafenib exhibited an altered expression of p53 and p73 isoforms, specifically increased expression of potentially prooncogenic Δ40p53β and a decreased level of tumor-suppressive TAp73β. Therefore, we propose that p53 family isoforms play a role in the aggressiveness of melanoma cells and could be a potential marker and target for melanoma therapy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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