Activation of sonic hedgehog signaling in oral squamous cell carcinomas: a preliminary study

Autor(es)

Cavicchioli Buim, Marcilei Eliza ^[1] ; Gurgel, Clarissa Araujo S. ^[2] ; Goncalves Ramos, Eduardo Antonio ^[2] ; Lourenco, Silvia Vanessa ^[3] ; Soares, Fernando Augusto ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Hosp AC Camargo Fund Antonio Prudente, Dept Anat Pathol, BR-01509900 Sao Paulo - Brazil

^[2] Fundacao Oswaldo Cruz, Lab Pathol & Mol Biol, BR-05508000 Salvador - Brazil

^[3] Univ Sao Paulo, Dept Gen Pathol, Sch Dent, BR-40296710 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: HUMAN PATHOLOGY; v. 42, n. 10, p. 1484-1490, OCT 2011.
• Citações Web of Science: 15

Resumo

Sonic hedgehog signaling is important for human development, and aberrant regulation of this pathway can result in the development of tumors. The aim of this study was to examine the expression of sonic hedgehog signaling molecules in oral squamous cell carcinoma. By quantitative real-time polymerase chain reaction, the expression of SHH, SMO, PTCH-1, and GLI-1 was analyzed in 30 oral squamous cell carcinoma cases and 8 samples of nonneoplastic oral mucosa and associated to clinical pathologic features. The expression of beta-catenin, cyclin D1, Wnt-1, and Egfr was evaluated by immunohistochemistry in 26 available cases of oral squamous cell carcinoma. Normal oral mucosa from healthy individuals was negative for all genes that were evaluated. SHH, PTCH-1, SMO, and GLI-1 were not expressed in nonneoplastic oral mucosa, and low levels of GLI-1 were observed in nonneoplastic oral mucosa that was adjacent to the tumor. All oral squamous cell carcinoma cases expressed high levels of PTCH-1, SMO, and GLI-1 and were devoid of SHH. The expression of SMO was associated with clinical stage (P = .022) and a borderline association in cervical lymph node metastasis (P = .053). PTCH-1 expression showed a strong correlation with SMO (rs = 0.64; P < .001) and GL-1 (rs = 0.70; P < .001); SMO and GLI-1 also correlated with each other (rs, 0.55; P < .001). All proteins evaluated were expressed as cyclin D1 (92% of samples), beta-catenin (73%), Egfr (46%), or Wnt-1 (32%). Our data demonstrate that sonic hedgehog signaling is activated in oral squamous cell carcinoma and suggest that this pathway mediates its tumorigenesis. (C) 2011 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 07/50609-0 - Validation of molecular classifiers ín head and neck
• Beneficiário: Marcilei Eliza Cavicchioli Buim
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs