Altered Expression of Shorter p53 Family Isoforms Can Impact Melanoma Aggressiveness
| Autor: | Nicolò Gavioli, Ignacija Vlašić, Yari Ciribilli, Petar Ozretić, Martina Radić, Giulia Barban, Neda Slade, Nikolina Hanžić, Lia Pinto, Ana Tadijan, Lidija Škreblin, Francesca Precazzini |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
p53 Cancer Research medicine.medical_treatment Resistance p73 Isoforms Melanoma P53 P73 Targeted therapy Δ160p53 Biology Article resistance Null cell medicine melanoma Vemurafenib neoplasms RC254-282 isoforms Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease targeted therapy Chromatin Oncology Cutaneous melanoma Cancer research Skin cancer medicine.drug |
| Zdroj: | Cancers Cancers, Vol 13, Iss 5231, p 5231 (2021) Volume 13 Issue 20 |
| Popis: | Cutaneous melanoma is the most aggressive form of skin cancer. Despite the significant advances in the management of melanoma in recent decades, it still represents a challenge for clinicians. The TP53 gene, the guardian of the genome, which is altered in more than 50% of human cancers, is rarely mutated in melanoma. More recently, researchers started to appreciate the importance of shorter p53 isoforms as potential modifiers of the p53-dependent responses. We analyzed the expression of p53 and p73 isoforms both at the RNA and protein level in a panel of melanoma-derived cell lines with different TP53 and BRAF status, in normal conditions or upon treatment with common anti-cancer DNA damaging agents or targeted therapy. Using lentiviral vectors, we also generated stable clones of H1299 p53 null cells over-expressing the less characterized isoforms Δ160p53α, Δ160p53β, and Δ160p53γ. Further, we obtained two melanoma-derived cell lines resistant to BRAF inhibitor vemurafenib. We observed that melanoma cell lines expressed a wide array of p53 and p73 isoforms, with Δ160p53α as the most variable one. 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 moreover, all Δ160p53 isoforms can stimulate proliferation and in vitro migration. Lastly, vemurafenib-resistant melanoma cells showed an altered expression of p53 and p73 isoforms, namely an increased expression of potentially pro-oncogenic Δ40p53β and a decrease in tumor-suppressive TAp73β. We therefore propose that p53 family isoforms can play a role in melanoma cells’ aggressiveness. |
| Databáze: | OpenAIRE |
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