engleski

The expression of p53/p73 isoforms, nm23/NDPK and Gli in MEL505 melanoma cell line upon gamma-irradiation

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, nm23/NDPK and GLI families of proteins. Therefore, we studied the expression profile of p53 and its potential interaction partners in human melanoma cell line Mel 505 upon γ irradiation. The results demonstrate an only slight change in expression of all p53 isoforms in cells irradiated with the dose of 5 Gy. 10 Gy irradiation elevated the expression of some isoforms (p53α, Δ40p53α and Δ133p53β). The levels of TAp73 isoforms expression remained unchanged upon irradiation in contrast to ΔNp73α and ΔNp73β whose expression was significantly increased in the period 6 to 12 hours after radiation even with lower dosages. 5 Gy irradiation does not significantly alter the expression level of Nm23/NDPK-H1 and Nm23/NDPK-H2, but when the cells were irradiated with 10 Gy the expression was elevated up to three times. Interesting was the level of GLI2 expression, showing time and dose response. It was more pronounced with higher dose of 10 Gy, implying dynamic balance which also includes levels of GLI3 activator and repressor forms. The obtained data showed 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.

melanoma cell line; γ irradiation; p53; p73; Nm23/NDPK; GLI

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