title: MAGEA4 induces growth in normal oral keratinocytes by inhibiting growth             arrest and apoptosis.
abstract: Cancer testis antigens (CTAs) are proteins that are normally expressed only             in male germ cells and are aberrantly upregulated in a variety of cancers such             as melanomas and lung cancer. MAGEA proteins belong to Class I CTAs and are being             utilized as targets for cancer immunotherapy. Despite the discovery of the first             CTA (MAGEA1) 20 years ago, the functions of these proteins remain poorly understood             and evidence suggests both oncogenic as well as tumor suppressive roles for these             proteins. Herein, we investigated the role of MAGEA4 in promoting cell growth.             When overexpressed, MAGEA4 promotes growth of spontaneously transformed normal             oral keratinocytes (NOK-SI). To understand the mechanism of growth stimulation             by MAGEA4, we explored the effect of overexpressing MAGEA4 on cell cycle and apoptosis.             MAGEA4 inhibits growth arrest of cells in the G1 phase of the cell cycle. We also             found that overexpression of MAGEA4 inhibits G418-induced apoptosis of NOK-SI             cells. Interestingly, this inhibition was accompanied by repression of two p53             downstream genes, BAX and CDKN1A. Our results indicate that MAGEA4 promotes growth             by preventing cell cycle arrest and by inhibiting apoptosis mediated by the p53             transcriptional targets.
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors: Sheetal
authors: S
authors: Bhan
authors: Alice
authors: A
authors: Chuang
authors: Sandeep S
authors: SS
authors: Negi
authors: Chad A
authors: CA
authors: Glazer
authors: Joseph A
authors: JA
authors: Califano
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005786:Gene Expression Regulation; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology; D009055:Mouth / Q000166:cytology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C095204:MAGEA4 protein, human; D009363:Neoplasm Proteins; D051028:bcl-2-Associated X Protein