Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma.
 ...
PMID:Generation of human melanocytes from induced pluripotent stem cells. 2124 4

Cutaneous melanomas may be quite heterogeneous in their clinical, histological and molecular findings. Correlating these features may help identify distinctive subgroups of melanomas and improve our overall understanding and prognostication of melanoma. We recently identified a subgroup of melanomas with increased chromosomal copy number gains in 8q24 at MYC having several distinctive clinical and histopathological characteristics, including an aggressive clinical course and an amelanotic clinical and histological appearance. It has been postulated that oncogenes such as MYC may have regulatory effects on genes critical to melanin pigment synthesis, specifically microphthalmia-associated transcription factor (MITF), which is known to have a key role in regulating the expression of tyrosinase (TYR), an important enzyme in the production of melanin pigment. We investigated the possible mechanism underlying the amelanotic appearance of melanomas with gains in 8q24 by evaluating the relationship between melanomas with and without 8q24 copy number gains and c-MYC, MITF and TYR protein expression. Immunohistochemical analysis of c-MYC, MITF and TYR was performed on 36 melanomas with gains in 8q24 and 40 melanomas without gains in 8q24. The melanomas with gains of 8q24 correlated with elevated c-MYC protein expression and melanomas without gains in 8q24 showed significantly decreased c-MYC protein expression. A direct relationship between the presence of gains in 8q24 and decreased MITF expression, as well as between c-MYC and TYR protein expression was also observed. Our results suggest that MYC can have a role in the pigmentary pathway of melanoma. In amelanotic melanomas with gains in 8q24, downregulation of TYR and other melanocyte-specific genes may be mediated by MYC leading to transcriptional suppression of MITF. As MITF is a frequently used marker to establish melanocytic lineage in melanoma, our study also raises the important clinical consideration that amelanotic melanomas, especially those with gains in 8q24 may lack expression of MITF.
 ...
PMID:The role of 8q24 copy number gains and c-MYC expression in amelanotic cutaneous melanoma. 2255 75