Investigation Into The Roles And Its Mechanism Of PTEN On Oral Squamous Cell Cancer And Precancerous Lesion

Oral squamous cell carcinoma (OSCC) is one of the most common oral cancer,which is a serious threat to human health with a very high morbidity and a low viability. Carcinogenesis must be understood in terms of accumulation of mutation in regulatory genes, including activation of oncogenes and inactivation or loss of tumor suppressor genes. As a result, gene diagnosis and gene therapy have been paid more attention day by day.PTEN gene is a new tumor suppressor gene found in 1997, which is identified on human chromosome 10q23.3. It is the first found tumor suppressor gene to have lipid phosphatase activity up to now. Many tumors have been found to have abnormal expressions of PTEN gene.In this study, PTEN protein expression in paraffin embedded tissues from 10 cases of normal oral mucosa,10 cases of oral epithelial hyperplasia,15 cases of oral epithelial dysplasia and 32 cases of OSCC was analysed by immunohistochemical method,and the relationship between the loss of expression of PTEN and the OSCC development and malignancy was investigated. The ukaryotic expression vector pcDNA-PTEN and vacant vector pcDNA3.1(+) were transferred in human carcinoma cell line Tca8113. Screened by G418 for a week, all of the control group cell without pcDNA-PTEN died and there was positive cell clone in the subject group cell with pcDNA-PTEN . The result of detection of PTEN mRNA and its protein in human carcinoma cell line Tca8113 showed PTEN gene had been transferred in the cell line successfully. Then we observed the effect of PTEN gene on Tca8113 cell growth and apoptosis by measuring the growth curve and flow cytometry.Results: Normal oral mucosa and oral epithelial hyperplasia tissues were all positive for PTEN protein .In the tissues from oral epithelial dysplasia,93.3% were positive for PTEN protein .In the tissues from OSCC,71.9% were positive for PTEN protein,28.1% were lacked for PTEN protein .PTEN protein expression did not show correlation to sex and age, but there was a significant difference between well differentiated OSCC(85.7% PTEN positive) and poorly differentiated OSCC(33.3% PTEN positive).The ukaryotic expression vector pcDNA-PTEN was identified by PCR and digestion to be constructed successfully and can be used in gene transferring. The result of growth curve and flow cytometry showed that exogenous PTEN gene had suppressed growth of carcinoma cell line and accelerated apoptosis. The suppression of carcinoma cell growth occurred from G1 phrase to S phrase.Conclusions: Loss of PTEN protein expression occurs increasingly commonly during the genesis and development of OSCC . The incidence of negative expression of PTEN protein is higher in poorly differentiated OSCC. This protein may help the identification of OSCC's pathologic grade. The exogenous PTEN gene suppresses growth of carcinoma cell line Tca8113 significantly and accelerates apoptosis. So PTEN may play an important role in gene diagnosis and gene therapy of oral carcinoma.