Proteomic characteristics of the giant congenital melanocytic nevi
Dept. of Medicine/박사
Proteomic Characteristics of the Giant Congenital Melanocytic NeviYong Kyu KimDepartment of MedicineThe Graduate School, Yonsei University(Directed by Professor Kwan Chul Tark)Background: Giant congenital melanocytic nevi (GCMN) are distress to patients and parents for two reasons. One is disfigurement and the other is possibility of malignant change. But development of GCMN and the underlying mechanism of melanotumorigenesis in GCMN are unknown.Objective: The aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN.Methods: We harvested 6 GCMN skins and 6 normal skins which were harvested from 3 GCMN donor patient and 3 from normal patient who were treated in plastic surgery department. Mean age of patient is 8.9 years. Group 1 samples include 3 GCMN and 3 normal skin samples(2 matched skins and 1 normal skin) which were used for proteomic analysis with One dimensional liquid chromatography mass spectrometry(1D-LC MS/MS) analysis and Group 2 samples include 3 GCMN and 3 normal skin samples( 2 normal skins and 1 matched skin) were used for western blotting analysis.The properties of the differentially expressed proteins (DEPs) were then further analyzed using the bioinformatics tools STRING, PANTHER, and ClueGO.Results: Among the total proteins in GCMN, changes in the expression of 50 were found to be DEPs significantly (p < 0.05, student t-test) down (4 proteins) or upregulated (46 proteins). Among the DEPs with a molecular function, chaperone proteins (15.7% of total DEPs) were the most highly altered, whereas among the DEPs involved in biological processes, alterations were mostly seen in signal transduction proteins (15.3% of total DEPs). Specifically, neurotrophin signaling, melanosome, and downregulated of MTA-3 in ER-negative breast tumors proteins were maximally implicated. Moreover, increases in the expression of members of the 14-3-3 protein family appeared be associated with key cellular biological functions in GCMN. Among the five isoforms of the 14-3-3 family (alpha, beta, zeta, epsilon, and tau), western blot analysis confirmed the upregulation of 14-3-3 epsilon in GCMN.Conclusion: We found the intensive alteration of 14-3-3 family proteins as a possible key regulator of GCMN biological pathway remodeling, which has important role in development of GCMN and could be associated with melanotumorigenesis.