RESUMO
AIM: The aim of this study was to analyse allelic loss of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene and its protein immuno-expression in dysplastic oral lesions and oral squamous cell carcinomas (OSCCs). METHODS AND RESULTS: Samples were collected from 153 patients [20 ranulas used as a control (C); 30 leucoplakias with mild dysplasia (MD); 30 leucoplakias with moderate to severe dysplasia (MSD); 73 oral squamous cell carcinoma (OSCC)]. PTEN protein expression was investigated using immunohistochemistry, and PTEN allelic loss was analysed by fluorescence in-situ hybridisation (FISH). Differences among groups were evaluated using the χ2 test. PTEN expression was higher in MSD (P = 0.002) and OSCC (P = 0.0259) compared with the C group; additionally, a higher expression was observed in MSD (P = 0.0035) and OSCC (P = 0.049) than MD. Regarding FISH analysis, a higher hemizygous (single copy) loss was observed in OSCC than in C (P = 0.0467) and in OSCC than in MD (P = 0.0175), as well as a higher homozygous deletion in OSCC compared with C (P = 0.0159) and OSCC than MD (P = 0.0145). CONCLUSION: The results of this work suggest that PTEN allelic loss is an important mechanism in the late stage of the development of oral potentially malignant lesions into oral cancer.
Assuntos
Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Neoplasias de Cabeça e Pescoço/genética , Leucoplasia Oral/genética , Neoplasias Bucais/genética , PTEN Fosfo-Hidrolase/genética , Lesões Pré-Cancerosas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVES: The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein. MATERIAL AND METHODS: Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF. RESULTS: Treatment with EGF resulted in increased levels of Akt, PTEN and p53 in all cell lineages. The expression of Mdm2 was constant in HN30 and HN6 lineages, while in HN19 showed slightly decreased expression. Under the action 17-AAG, in HN6 and HN19, the expression of PTEN and p53 proteins was suppressed, while Akt and Mdm2 expression was reduced. Finally, in the HN30 cell lineage were absolute absence of expression of Akt, Mdm2 and p53 and decreased expression of PTEN. CONCLUSION: These data allow us to speculate on the particular utility of 17-AAG for HNSCC treatment through the inhibition of Akt protein expression, especially in the cases that retain the expression of PTEN protein.