Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis
Melanoma antigen A4 is expressed in non-small cell lung cancers and promotes apoptosis
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DOI：
10.1158/0008-5472.can-05-3327
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发表时间：
2006-05-01
期刊：
影响因子：
11.2
通讯作者：
Comhair, SAA
中科院分区：
文献类型：
--
作者：
Peikert, T;Specks, U;Comhair, SAA
多种黑色素瘤抗原A（MAGE-A）基因在非小细胞肺癌中常见。它们的生物学功能尚未得到很好的表征，但可能涉及细胞凋亡和细胞周期进程的调节。我们推测MAGE-A4参与细胞凋亡的调节。为了研究这一点，评估了MAGE-A的表达。MAGE-A4在48%的非小细胞肺癌中表达。90%的表达MAGE-A4的肺癌被分类为鳞状细胞癌，10%为腺癌。无肿瘤的周围肺组织对MAGE-A4呈阴性。在人胚肾细胞（293细胞）中稳定表达源自人肺癌的MAGE-A4的分子克隆，以评价对细胞死亡的影响。MAGE-A4的过表达增加了细胞凋亡指数（P < 0.0001）和caspase-3活性（P < 0.002）。25 μ mol/L足叶乙甙（一种化疗药物）可增加凋亡效应（P < 0.0001）。此外，我们发现，使用小干扰RNA方法沉默MAGE-A4导致鳞状细胞肺癌细胞系H1703中caspase-3活性降低58%（P = 0.0027），293/ MAGE-A4细胞中caspase-3活性降低24%（P = 0.028）。这些发现表明，MAGE-A4表达可能促进肿瘤细胞死亡，使恶性肿瘤对凋亡刺激物（如化疗剂）敏感，因此可能代表肿瘤抑制蛋白。
A variety of melanoma antigen A (MAGE-A) genes are commonly detected in non-small cell lung cancers. Their biological function is not well characterized but may involve the regulation of apoptosis and cell cycle progression. We hypothesized that MAGE-A4 is involved in the regulation of apoptosis. To investigate this, expression of MAGE-A was evaluated. MAGE-A4 was expressed in 48% of non-small cell lung carcinomas. Ninety percent of lung carcinomas expressing MAGE-A4,were classified as squamous cell carcinomas and 10% were adenocarcinomas. Tumor-free surrounding lung tissue was negative for MAGE-A4. A molecular clone of MAGE-A4 derived from human lung cancer was stably expressed in human embryonic kidney cells (293 cells) to evaluate effects on cell death. Overexpression of MAGE-A4 increased apoptosis as measured by the apoptotic index (P < 0.0001) and caspase-3 activity (P < 0.002). Exposure to 25 mu mol/L etoposide, a chemotherapeutic agent, increased the apoptotic effect (P < 0.0001). Furthermore, we show that MAGE-A4 silencing using a small interfering RNA approach results in decreased caspase-3 activity in the squamous cell lung cancer cell line H1703 by 58% (P = 0.0027) and by 24% (P = 0.028) in 293/ MAGE-A4 cells. These findings suggest that MAGE-A4 expression may promote tumor cell death, sensitize malignancies to apoptotic stimuli, such as chemotherapeutic agents, and therefore may represent a tumor suppressor protein.