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HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways

Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other...

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Autores principales: Miranda da Costa, Natacha Malu, Saab Abe, Caio Tadashi, Mitre, Geovanni Pereira, Mesquita, Ricardo Alves, da Silva Kataoka, Maria Sueli, Ribeiro Ribeiro, André Luis, Jaeger, Ruy Gastaldoni, Alves-Júnior, Sérgio de Melo, Smith, Andrew Mark, Pinheiro, João de Jesus Viana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678339/
https://www.ncbi.nlm.nih.gov/pubmed/31319505
http://dx.doi.org/10.3390/cells8070731
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author Miranda da Costa, Natacha Malu
Saab Abe, Caio Tadashi
Mitre, Geovanni Pereira
Mesquita, Ricardo Alves
da Silva Kataoka, Maria Sueli
Ribeiro Ribeiro, André Luis
Jaeger, Ruy Gastaldoni
Alves-Júnior, Sérgio de Melo
Smith, Andrew Mark
Pinheiro, João de Jesus Viana
author_facet Miranda da Costa, Natacha Malu
Saab Abe, Caio Tadashi
Mitre, Geovanni Pereira
Mesquita, Ricardo Alves
da Silva Kataoka, Maria Sueli
Ribeiro Ribeiro, André Luis
Jaeger, Ruy Gastaldoni
Alves-Júnior, Sérgio de Melo
Smith, Andrew Mark
Pinheiro, João de Jesus Viana
author_sort Miranda da Costa, Natacha Malu
collection PubMed
description Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior.
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spelling pubmed-66783392019-08-19 HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways Miranda da Costa, Natacha Malu Saab Abe, Caio Tadashi Mitre, Geovanni Pereira Mesquita, Ricardo Alves da Silva Kataoka, Maria Sueli Ribeiro Ribeiro, André Luis Jaeger, Ruy Gastaldoni Alves-Júnior, Sérgio de Melo Smith, Andrew Mark Pinheiro, João de Jesus Viana Cells Article Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior. MDPI 2019-07-17 /pmc/articles/PMC6678339/ /pubmed/31319505 http://dx.doi.org/10.3390/cells8070731 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Miranda da Costa, Natacha Malu
Saab Abe, Caio Tadashi
Mitre, Geovanni Pereira
Mesquita, Ricardo Alves
da Silva Kataoka, Maria Sueli
Ribeiro Ribeiro, André Luis
Jaeger, Ruy Gastaldoni
Alves-Júnior, Sérgio de Melo
Smith, Andrew Mark
Pinheiro, João de Jesus Viana
HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title_full HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title_fullStr HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title_full_unstemmed HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title_short HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways
title_sort hif-1α is overexpressed in odontogenic keratocyst suggesting activation of hif-1α and notch1 signaling pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678339/
https://www.ncbi.nlm.nih.gov/pubmed/31319505
http://dx.doi.org/10.3390/cells8070731
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