Down-regulation of methylthioadenosine phosphorylase in malignant BERP35T-2 cells and in non-small cell lung cancers

Objective: The aim of this study was to investigate the expression alteration of MTAP gene in tumorigenesis of bronchial epithelial cell line and Chinese non-small lung cancers. Methods: Total protein from BEP2D and BERP35T-2 cells was extracted and analyzed by 2-D electrophoresis and peptide mass fingerprinting spectrum. Northern blot was performed to confirm differences of expression of MTAP gene between BEP2D and BERP35T-2. RT-PCR was used to observe the mRNA expression of MTAP in 15 clinical cases with non-small cell lung cancer. Results: MTAP was found to be expressed at lower level in malignant BERP35T-2 cells than in BEP2D analyzed by 2-dimensional electrophoresis, which was confirmed at transcriptional level by Northern blot. In 11 out of 15 NSCLC samples analyzed by RT-PCR, MTAP expression was down-regulated. MTAP was poorly expressed in 90.9% of mild/poorly differentiated NSCLC cases, while in 25% of well-differentiated cases. Conclusion: The result of this study indicates that the down-regulations of MTAP at protein level or mRNA level in Chinese NSCLC might contribute to the carcinogenesis of lung and MTAP might be a candidate of tumor suppressor gene. (authors)