Human giant congenital melanocytic nevus exhibits potential proteomic alterations leading to melanotumorigenesis.
BACKGROUND
A giant congenital melanocytic nevus (GCMN) is a malformation of the pigment cells. It is a distress to the patients for two reasons: one is disfigurement, and the other is the possibility of malignant changes. However, the underlying mechanisms of the development of GCMN and melanotumorigenesis in GCMN are unknown. Hence, the aim of this study was to identify the proteomic alterations and associated functional pathways in GCMN.


RESULTS
Proteomic differences between GCMN (n = 3) and normal skin samples (n = 3) were analyzed by one-dimensional-liquid chromatography-tandem mass spectrometry Relative levels of the selected proteins were validated using western blot analysis. The biological processes associated with the abundance modified proteins were analyzed using bioinformatic tools. Among the 46 abundance modified proteins, expression of 4 proteins was significantly downregulated and expression of 42 proteins was significantly upregulated in GCMN compared to normal skin samples (p < 0.05). More importantly, 31% of the upregulated proteins were implicated in various cancers, with five proteins being specifically related with melanoma. The abundance modified proteins in GCMN were involved in the biological processes of neurotrophin signaling, melanosome, and downregulated of MTA-3 in ER-negative breast tumors. In particular, an increase in the expression of the 14-3-3 protein family members appeared to be associated with key cellular biological functions in GCMN. Western blot analysis confirmed the upregulation of 14-3-3epsilon, 14-3-3 tau, and prohibitin in GCMN.


CONCLUSIONS
These findings suggest that GCMN exhibits potential proteomic alterations, which may play a role in melanotumorigenesis, and the significant alteration of 14-3-3 family proteins could be a key regulator of the biological pathway remodeling in GCMN.
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Hyoung Kyu
HK
Kim
Apgujung YK Plastic Surgery Center, Seoul, Korea.
Yong Kyu
YK
Kim
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
In-Sung
IS
Song
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Sung-Ryul
SR
Lee
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Seung Hun
SH
Jeong
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Min Hee
MH
Kim
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Dae Yun
DY
Seo
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Nari
N
Kim
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Byoung Doo
BD
Rhee
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Kyoung Soo
KS
Ko
Department of Plastic and Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Korea.
Kwan Chul
KC
Tark
Department of Plastic and Reconstructive Surgery, National Medical Center, Seoul, Korea.
Chul Gyoo
CG
Park
Department of Veterinary Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, Korea.
Je-Yoel
JY
Cho
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea.
Jin
J
Han