title: Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.
abstract: BACKGROUND
  Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB).
  
  
  METHODS
  We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry.
  
  
  RESULTS
  We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521).
  
  
  CONCLUSIONS
  Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.
authors.affiliation: School of Dentistry of the Federal University of Bahia, Bahia, Brazil.
authors.forename: Clarissa Araújo Silva
authors.initials: CA
authors.lastname: Gurgel
authors.forename: Marcilei Eliza Cavichiolli
authors.initials: ME
authors.lastname: Buim
authors.forename: Kátia Cândido
authors.initials: KC
authors.lastname: Carvalho
authors.forename: Caroline Brandi Schlaepfer
authors.initials: CB
authors.lastname: Sales
authors.forename: Mitermayer Galvão
authors.initials: MG
authors.lastname: Reis
authors.forename: Renata Oliveira
authors.initials: RO
authors.lastname: de Souza
authors.forename: Ludmila
authors.initials: L
authors.lastname: de Faro Valverde
authors.forename: Roberto Almeida
authors.initials: RA
authors.lastname: de Azevedo
authors.forename: Jean Nunes
authors.initials: JN
authors.lastname: Dos Santos
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Eduardo Antônio Gonçalves
authors.initials: EA
authors.lastname: Ramos
mesh_terms: D000293:Adolescent; D000328:Adult; D000564:Ameloblastoma / Q000737:chemistry / Q000235:genetics*; D000565:Ameloblasts / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D053823:Hedgehog Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D008339:Mandibular Neoplasms / Q000737:chemistry; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000473:pathology; D009808:Odontogenic Tumors / Q000737:chemistry / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000032:analysis; D014158:Transcription, Genetic / Q000235:genetics*; D055815:Young Adult; D000071676:Zinc Finger Protein GLI1
chemical_list: C530104:CCND1 protein, human; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C509239:SHH protein, human; C491023:SMO protein, human; C490764:SUFU protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D019938:Cyclin D1
keywords: ameloblastoma; keratocystic odontogenic tumor; odontogenic tumors; sonic hedgehog