Cargando…

Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1

BACKGROUND: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. AIMS: To evaluate the difference of hypoxic gene expression signatures in primary mel...

Descripción completa

Detalles Bibliográficos
Autores principales: Ercin, Mustafa Emre, Bozdoğan, Önder, Çavuşoğlu, Tarık, Bozdoğan, Nazan, Atasoy, Pınar, Koçak, Mukadder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Galenos Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934014/
https://www.ncbi.nlm.nih.gov/pubmed/31594284
http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2019.3.145
_version_ 1783483324749053952
author Ercin, Mustafa Emre
Bozdoğan, Önder
Çavuşoğlu, Tarık
Bozdoğan, Nazan
Atasoy, Pınar
Koçak, Mukadder
author_facet Ercin, Mustafa Emre
Bozdoğan, Önder
Çavuşoğlu, Tarık
Bozdoğan, Nazan
Atasoy, Pınar
Koçak, Mukadder
author_sort Ercin, Mustafa Emre
collection PubMed
description BACKGROUND: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. AIMS: To evaluate the difference of hypoxic gene expression signatures in primary melanoma cell lines and metastatic melanoma cell lines and to find the expression changes of hypoxia-related genes in primary melanoma cell lines at experimental hypoxic conditions. STUDY DESIGN: Cell study. METHODS: The mRNA expression levels of hypoxia-related genes in primary melanoma cell lines and metastatic melanoma cell lines and at experimental hypoxic conditions in primary melanoma cell lines were evaluated by using real-time polymerase chain reaction. Depending on the experimental data, we focused on two genes/proteins, the hypoxia-inducible factor-1 beta and the N-myc downstream regulated gene-1. The expression levels of the two proteins were investigated by immunohistochemistry methods in 16 primary and metastatic melanomas, 10 intradermal nevi, and a commercial tissue array comprised of 208 cores including 192 primary and metastatic malignant melanomas. RESULTS: The real-time polymerase chain reaction study showed that hypoxic gene expression signature was different between metastatic melanoma cell lines and primary melanoma cell lines. Hypoxic experimental conditions significantly affected the hypoxic gene expression signature. In immunohistochemical study, N-myc downstream regulated gene-1 expression was found to be lower in primary cutaneous melanoma compared to in intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of hypoxia-inducible factor-1 beta was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between the two proteins studied in the study groups. CONCLUSION: Hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light on hypoxic processes in melanoma and unlock a Pandora’s box for development of new therapeutic strategies.
format Online
Article
Text
id pubmed-6934014
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Galenos Publishing
record_format MEDLINE/PubMed
spelling pubmed-69340142020-01-04 Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1 Ercin, Mustafa Emre Bozdoğan, Önder Çavuşoğlu, Tarık Bozdoğan, Nazan Atasoy, Pınar Koçak, Mukadder Balkan Med J Original Article BACKGROUND: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is, however, not well known in oncogenesis of malignant melanoma. AIMS: To evaluate the difference of hypoxic gene expression signatures in primary melanoma cell lines and metastatic melanoma cell lines and to find the expression changes of hypoxia-related genes in primary melanoma cell lines at experimental hypoxic conditions. STUDY DESIGN: Cell study. METHODS: The mRNA expression levels of hypoxia-related genes in primary melanoma cell lines and metastatic melanoma cell lines and at experimental hypoxic conditions in primary melanoma cell lines were evaluated by using real-time polymerase chain reaction. Depending on the experimental data, we focused on two genes/proteins, the hypoxia-inducible factor-1 beta and the N-myc downstream regulated gene-1. The expression levels of the two proteins were investigated by immunohistochemistry methods in 16 primary and metastatic melanomas, 10 intradermal nevi, and a commercial tissue array comprised of 208 cores including 192 primary and metastatic malignant melanomas. RESULTS: The real-time polymerase chain reaction study showed that hypoxic gene expression signature was different between metastatic melanoma cell lines and primary melanoma cell lines. Hypoxic experimental conditions significantly affected the hypoxic gene expression signature. In immunohistochemical study, N-myc downstream regulated gene-1 expression was found to be lower in primary cutaneous melanoma compared to in intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of hypoxia-inducible factor-1 beta was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between the two proteins studied in the study groups. CONCLUSION: Hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light on hypoxic processes in melanoma and unlock a Pandora’s box for development of new therapeutic strategies. Galenos Publishing 2020-01 2019-12-20 /pmc/articles/PMC6934014/ /pubmed/31594284 http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2019.3.145 Text en ©Copyright 2020 by Trakya University Faculty of Medicine http://creativecommons.org/licenses/by/2.5/ The Balkan Medical Journal published by Galenos Publishing House.
spellingShingle Original Article
Ercin, Mustafa Emre
Bozdoğan, Önder
Çavuşoğlu, Tarık
Bozdoğan, Nazan
Atasoy, Pınar
Koçak, Mukadder
Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title_full Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title_fullStr Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title_full_unstemmed Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title_short Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF-1β and NDRG-1
title_sort hypoxic gene signature of primary and metastatic melanoma cell lines: focusing on hif-1β and ndrg-1
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934014/
https://www.ncbi.nlm.nih.gov/pubmed/31594284
http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2019.3.145
work_keys_str_mv AT ercinmustafaemre hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1
AT bozdoganonder hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1
AT cavusoglutarık hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1
AT bozdogannazan hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1
AT atasoypınar hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1
AT kocakmukadder hypoxicgenesignatureofprimaryandmetastaticmelanomacelllinesfocusingonhif1bandndrg1