title: Role of HIF-1α and CASPASE-3 in cystogenesis of odontogenic cysts and tumors.
abstract: OBJECTIVE
  Odontogenic cysts and tumors are the most relevant lesions that affect the gnathic bones. These lesions have in common the formation of cystic areas and this common feature may suggest involvement of similar mechanisms. The hypoxia inducible factor 1 alpha (HIF-1α), a responsive protein to hypoxia and caspase-3, an irreversible apoptosis marker, may contribute to cyst formation. Thus, this study aimed to investigate the immunoexpression of these proteins in odontogenic cysts and tumors.
  
  
  METHODS
  Twenty cases of ameloblastoma, keratocystic odontogenic tumor (KOT) (n = 20), radicular cyst (RC) (n = 18), dentigerous cyst (DC) (n = 11), calcifying cystic odontogenic tumor (n = 8), and dental follicle (DF) (n = 10) were used to investigate HIF-1α and caspase-3 expression in sequential serial cuts by immunohistochemistry.
  
  
  RESULTS
  HIF-1α was overexpressed in RC, DC, and ameloblastoma when compared with DF. The basal and sometimes the lower suprabasal layer showed no or very low expression in DC, KOT, and ameloblastoma, the last also showing strong expression in solid epithelial areas and initial cystic formation regions. Caspase-3 was found to be overexpressed in all lesions, with the highest expression in odontogenic cysts compared to tumors. HIF-1α and caspase-3 were localized in similar areas of the same lesions, especially in the epithelium surrounding cystic formations.
  
  
  CONCLUSIONS
  This study showed distinct immunoexpression of HIF-1α and caspase-3 in odontogenic cyst and tumors, with higher expression observed in odontogenic cysts.
  
  
  CONCLUSIONS
  These findings suggest a possible correlation between hypoxia, apoptosis, and cystogenesis, leading to understand the mechanisms responsible to cystic formation in odontogenic lesions.
authors.affiliation: Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Rua Augusto Corrêa, 01, Guamá, Belém, PA, 66075110, Brazil.
authors.forename: Natacha M M
authors.initials: NMM
authors.lastname: da Costa
authors.affiliation: School of Dentistry, Universidade Positivo, Av. Prof. Pedro Viriato Parigot de Souza, 5300, Curitiba, PR, 80740-050, Brazil.
authors.forename: Adriane S
authors.initials: AS
authors.lastname: de Siqueira
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Center of Para-CESUPA, Belem, Brazil.
authors.forename: André L R
authors.initials: ALR
authors.lastname: Ribeiro
authors.affiliation: Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Rua Augusto Corrêa, 01, Guamá, Belém, PA, 66075110, Brazil.
authors.forename: Maria S
authors.initials: MS
authors.lastname: da Silva Kataoka
authors.affiliation: Department of Cell and Developmental Biology Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, Ed. Biomédicas 1, São Paulo, SP, 05508-000, Brazil.
authors.forename: Ruy G
authors.initials: RG
authors.lastname: Jaeger
authors.affiliation: Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Rua Augusto Corrêa, 01, Guamá, Belém, PA, 66075110, Brazil.
authors.forename: Sérgio M
authors.initials: SM
authors.lastname: de Alves-Júnior
authors.affiliation: Department of Microbial Diseases, Eastman Dental Institute, University College London, London, UK.|The Rayne Building, Centre for Molecular Medicine, 5 University Street, London, WC1E 6JF, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Smith
authors.affiliation: Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Rua Augusto Corrêa, 01, Guamá, Belém, PA, 66075110, Brazil. radface@hotmail.com.
authors.forename: João
authors.initials: J
authors.lastname: de Jesus Viana Pinheiro
mesh_terms: D000564:Ameloblastoma / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism*; D003795:Dental Sac / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D009807:Odontogenic Cysts / Q000378:metabolism*; D009808:Odontogenic Tumors / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053148:Caspase 3
keywords: Caspase-3; Cystogenesis; HIF-1α; Odontogenic cyst; Odontogenic tumors