Article
Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.
Registro en:
SANTOS, J. N. et al. Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma. Journal of Oral Pathology & Medicine, v. 43, n. 8, p. 619-626, 2014.
0904-2512
10.1111/jop.12180
Autor
Gurgel, Clarissa Araújo Silva
Buim, Marcilei Eliza Cavichiolli
Carvalho, Katia Cândido
Sales, Caroline Brandi Schlaepfer
Reis, Mitermayer Galvão dos
Souza, Renata Oliveira de
Valverde, Ludmila de Faro
Azevedo, Roberto Almeida de
Santos, Jean Nunes dos
Soares, Fernando Augusto
Ramos, Eduardo Antônio Gonçalves
Resumen
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: Weobserved 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.