Naslov
The Expression of p53/p73 Isoforms, NME and GLI in Metastatic Melanoma and Their Induction by γ-Irradiation

Autori
Hanžić, Nikolina ; Proust, Bastien Lucien Jean ; Petrović, Lidija ; Ozretić, Petar ; Milas, Ivan ; Herak Bosnar, Maja ; Levanat, Slade ; Slade, Neda

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

Izvornik
HDIR-4 - 4thMeeting with International Participation “From Bench to Clinic / Beketić-Orešković, L ; Kusić, Z ; Šarčević, B - Zagreb : Libri Oncologici, 2016, 18-18

Skup
HDIR-4 - 4thMeeting with International Participation “From Bench to Clinic

Mjesto i datum
Zagreb, Hrvatska, 03.11.2016. - 04.11.2016

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
p53, p73, NME, GLI, melanoma

Sažetak
Although mutations of p53 occur infrequently in melanoma, it fails to function as a tumor suppressor. This may result from alterations in p53 family members, including the diverse isoforms of p53 and its homologue p73. Moreover, we assume that the p53 function in malignant melanoma might be altered through interactions with p53 small molecular weight and p73 isoforms, NME and GLI families of proteins. Therefore, we are studying the 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 30 patients with metastatic melanoma, the expression of p53, p73, NME and GLI protein families was determined by western blot analysis and quantitative RT-PCR. Protein expression analysis has shown that only Δ133p53α expression is significantly different in the two tissue types: it is poorly expressed in healthy tissue (only 12% of samples), but strongly expressed in tumor tissue (72% of samples). There is no difference of expression of other p53 isoforms between healthy and tumor tissue samples. Protein p73 is expressed in almost all tumor samples and healthy tissue samples. TAp73α and ΔNp73α, are more frequent in tumor samples and TAp73 β and ΔNp73 β, are less frequent in tumor samples than in healthy tissue samples. Proteins NME1 and NME3 are expressed in 96% of tumor samples and 70% of healthy tissue samples. Surprisingly, protein expression of NME1 and NME2 was several fold higher in tumor samples than in healthy tissue samples. GLI1 and both GLI3A and GLI3R have higher expression in tumor than in healthy tissue samples. GLI2 is expressed in only 8% of tumors and not in healthy tissue samples. Comparison of gene expression in the melanoma tissue samples and corresponding normal tissue revealed that NME2 is significantly stronger expressed in normal tissue while NME1 is expressed equally in healthy and tumor tissue. All other examined genes are significantly less expressed in the tumor tissue. To obtain higher expression of proteins of interest, we irradiated two melanoma cell lines with different mutational status of p53 (Mel505/p53mut and A375M/p53wt) with γ rays with the dose of 5 and 10 Gy. The results have shown that γ irradiation increases the level of proteins of interest to certain extent and their protein expression profile obtained after γ irradiation provide the molecular environment where the proteins possibly interact and inhibit activity of p53 in melanoma.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA