Patched 1 expression in Merkel cell carcinoma.
Gene expression
Hedgehog signaling
Merkel cell carcinoma
Merkel cell polyomavirus
Patched 1 | Gene expression
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
28
07
2020
accepted:
18
08
2020
pubmed:
13
11
2020
medline:
15
5
2021
entrez:
12
11
2020
Statut:
ppublish
Résumé
The relevance of Hedgehog signaling in Merkel cell carcinoma has only been addressed by a few studies with conflicting results. Thus, we aimed to establish the expression of Hedgehog signaling molecules in Merkel cell carcinoma to characterize causes of aberrant expression and to correlate these findings with the clinical course of the patients. Immunohistochemistry was performed for Sonic, Indian, Patched 1 (PTCH1) and Smoothened on patients' tumor tissue. Respective mRNA expression was analyzed in 10 Merkel cell carcinoma cell lines using quantitative real-time polymerase chain reaction. PTCH1 sequencing and DNA methylation microarray analyses were carried out on tumor tissues as well as cell lines. PTCH1 immunoreactivity in Merkel cell carcinoma was similar to that of basal cell carcinomas, which both significantly differed from PTCH1 immunoreactivity in healthy skin. Most PTCH1 mutations found were synonymous or without known functional impact. However, on average, the promoter regions of both PTCH1 were hypomethylated independently from PTCH1 gene expression or Merkel cell polyomavirus status. PTCH1 and GLI1/2/3 genes were differently expressed in different cell lines; notably, there was a significant correlation between GLI2 and PTCH1 mRNA expression. Similar to PTCH1 protein expression in patient tissues, PTCH1 gene expression in Merkel cell carcinoma cell lines is highly variable, but due to the similar methylation pattern across Merkel cell carcinoma cell lines, effects other than methylation seem to be the reason for the differential expression and PTCH1 appears to be upregulated by GLI as a classical Hedgehog target gene.
Identifiants
pubmed: 33180347
doi: 10.1111/1346-8138.15611
doi:
Substances chimiques
Hedgehog Proteins
0
PTCH1 protein, human
0
Patched-1 Receptor
0
Transcription Factors
0
Zinc Finger Protein GLI1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-74Subventions
Organisme : Medizinische Fakultät, Ruhr-Universität Bochum
ID : F855N2-2015
Organisme : Deutschen Konsortium für Translationale Krebsforschung
ID : ED003
Informations de copyright
© 2020 Japanese Dermatological Association.
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