The adherens junction-associated protein 1 is a negative transcriptional regulator of MAGEA2, which potentiates temozolomide-induced apoptosis in GBM

• Published in: International journal of oncology Vol. 44; no. 4; pp. 1243 - 1251
• Main Authors: ZENG, LIANG, KANG, CHUNSHENG, DI, CHUNHUI, FEE, BRIAN E, RIVAS, MIRIAM, LIN, JAMES, ADAMSON, DAVID CORY
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.04.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: adherens junction-associated protein-1; Adherens Junctions; Antigens; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; bcl-2-Associated X Protein - biosynthesis; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Cancer; Cancer therapies; Caspase 3 - metabolism; Caspase 7 - metabolism; Cell Adhesion Molecules - genetics; Cell cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Movement; Chemotherapy; Cytochrome; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Deoxyribonucleic acid; DNA; DNA methylation; Dosage and administration; Drug Resistance, Neoplasm; Gene expression; Gene Expression Regulation, Neoplastic; gene regulation; Genomes; glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Health aspects; HEK293 Cells; Histone Deacetylases - metabolism; Humans; In Situ Nick-End Labeling; MAGEA2; Medical prognosis; Melanoma-Specific Antigens - biosynthesis; migration; Mitochondria; Neoplasm Proteins - biosynthesis; Oncology, Experimental; Proteins; Studies; Temozolomide; Transcription factors; Transcription, Genetic; Tumor Suppressor Protein p53 - biosynthesis; Tumors; United States > US
• DOI: 10.3892/ijo.2014.2277
• ISSN: 1019-6439

Previous studies identified the frequent loss of adherens junction-associated protein 1 (AJAP1) expression in glioblastoma (GBM) and its correlation with worse survival. AJAP1 may suppress glioma cell migration, which plays an important role in tumor progression in malignant gliomas such as GBM. However, the role of AJAP1 in cell cycle arrest or apoptosis and resistance to chemotherapy remains unclear. Based on microarray screening results, quantitative PCR and luciferase plasmid reporter constructs were used to evaluate the possible regulatory role of AJAP1 on MAGEA2 expression and function. Cell death assays, TUNEL and other markers of apoptosis were utilized to detect cell apoptosis. Restoration of AJAP1 expression in glioma cells was analyzed after temozolomide exposure. AJAP1 suppressed the expression of MAGEA2 and inhibited the transcriptional activity of MAGEA2 in glioma cells. As AJAP1 expression decreased MAGEA2 protein expression apoptosis increased moderately. Consistent with increased cell death, the induced loss of MAGEA2 expression correlated with increased caspase 3/7 activity, BCL2/BAX ratio and TUNEL signal. AJAP1 expression enhanced cell death in the presence of temozolomide. This study suggests AJAP1 may also function as a pro-apoptotic factor and potentiate cell death by temozolomide in glioma cells. This effect may be partially explained by AJAP1-mediated gene regulation of MAGEA2.