Local Inhibition of MEK/Akt Prevents Cellular Growth in Human Congenital Melanocytic Nevi.
Animals
Antineoplastic Agents
/ administration & dosage
Cell Proliferation
/ drug effects
Child
Child, Preschool
Female
GTP Phosphohydrolases
/ genetics
Humans
Infant
Injections, Intradermal
Injections, Intralesional
MART-1 Antigen
/ metabolism
Male
Melanocytes
/ drug effects
Membrane Proteins
/ genetics
Mice
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Nevus, Pigmented
/ congenital
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
SOXE Transcription Factors
/ metabolism
Signal Transduction
/ drug effects
Skin
/ cytology
Skin Neoplasms
/ congenital
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
11
07
2018
revised:
20
03
2019
accepted:
26
03
2019
pubmed:
7
5
2019
medline:
17
6
2020
entrez:
7
5
2019
Statut:
ppublish
Résumé
The management of large congenital melanocytic nevi (lCMN) is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of mitogen-activated protein kinase and phosphoinositide 3-kinase (Akt) pathways. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and Akt inhibitors reduced the nevosphere diameter in sphere-forming assays, as well as cell viability and proliferation in in vitro assays. Standardized lCMN explants were then cultured ex vivo with the same inhibitors, which induced a decrease in MelanA+ and Sox10+ cells in both epidermis and dermis. Finally, intradermal injections of these inhibitors were administered within standardized lCMN xenografts in Rag2
Identifiants
pubmed: 31059696
pii: S0022-202X(19)31499-X
doi: 10.1016/j.jid.2019.03.1156
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
MART-1 Antigen
0
MLANA protein, human
0
Membrane Proteins
0
SOX10 protein, human
0
SOXE Transcription Factors
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2004-2015.e13Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.