ISSN : 2146-3123
E-ISSN : 2146-3131

Hypoxic Gene Signature of Primary and Metastatic Melanoma Cell Lines: Focusing on HIF1-Beta and NDRG-1
Mustafa Emre Ercin1, Önder Bozdoğan2, Tarık Çavuşoğlu3, Nazan Bozdoğan4, Pınar Atasoy5, Mukadder Koçak6
1Department of Pathology, Karadeniz Technical University School of Medicine, Trabzon, Turkey
2Clinic of Pathology, University of Health Sciences, Ankara Numune Training and Research Hospital, Ankara, Turkey
3Private Practice
4Clinic of Pathology, University of Health Sciences, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
5Department of Pathology, Kırıkkale University School of Medicine, Kırıkkale, Turkey
6Clinic of Dermatology, LÖSEV-LÖSANTE Children and Adult Hospital, Arkara, Turkey
DOI : 10.4274/balkanmedj.galenos.2019.2019.3.145

Background: Hypoxia is an important microenvironmental factor significantly affecting tumor proliferation and progression. The importance of hypoxia is not well known in oncogenesis of malignant melanoma.
Aims: To evaluate the difference of hypoxia related gene expressions signature in primary and metastatic melanoma cell lines and to find the expression changes of hypoxia related genes in primary melanoma cell lines at experimental hypoxia conditions.
Study Design: Experimental study
Methods: The mRNA expression levels of hypoxic genes in primary and metastatic melanoma cell lines and in primary cell line at experimental hypoxia conditions were evaluated by using real-time PCR. Depend on experimental data, we focused on two gene/protein, Hypoxia-inducible Factor-1 Beta (HIF-1β) and N-Myc Downstream Regulated 1 (NDRG1). The protein expression levels of two proteins were investigated by immunohistochemistry methods, in 16 primary and metastatic melanomas, 10 intradermal nevi, and commercial tissue array comprised of 208 cores, including 192 primary and metastatic malignant melanomas.
Results: The real-time PCR study showed that hypoxic gene expression signature was different between metastatic and primary cell lines. Hypoxic experimental conditions significantly affect hypoxic gene expression signature. In immunohistochemical study, NDRG-1 expression was found to be lower in primary cutaneous melanoma compared to intradermal nevi (p=0.001). In contrast, the cytoplasmic expression of HIF-1β was higher in primary cutaneous melanoma than in intradermal nevi (p=0.001). We also detected medium/strong significant correlations between studied two proteins in the study groups.
Conclusion: This study may show that hypoxic response consists of closely related proteins in more complex pathways. These findings will shed light to hypoxic processes in melanoma and unlock “Pandora’s box” for development of new therapeutic strategies.

Keywords : HIF-1 beta, hypoxia, melanoma, NDRG1
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