Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology.
Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology.
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DOI：
10.1016/j.acthis.2011.12.006
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发表时间：
2012-11
影响因子：
2.5
通讯作者：
Taylor K
中科院分区：
文献类型：
--
作者：
Cuajungco MP;Podevin W;Valluri VK;Bui Q;Nguyen VH;Taylor K
跨膜(TMEM)-176A和176B蛋白属于MS4A蛋白家族，其在免疫系统中的功能尚不清楚。TMEM176A转录本先前被证明在肝癌或蛋白尿肾组织中升高，而TMEM176B转录本在耐受异体组织移植和肿瘤成纤维细胞中发现显著变化。为了研究人类TMEM176A和176B之间的功能关系及其与癌症的推定联系，我们使用了聚合酶链反应和生化分析。在这里，我们发现TMEM176A和176B在所有被检测的人体组织中广泛表达。异种表达的TMEM176A和176B的共免疫沉淀显示了直接的物理相互作用。为了确定这种相互作用与癌症病理的相关性，我们分析了来自各种正常和癌症组织的活检组织样本。我们的数据显示，人类TMEM176A和176B蛋白水平在淋巴瘤中显著升高，而在正常组织中没有。TMEM176A蛋白水平在肺癌中也显著升高。最后，对TMEM176A / 176B蛋白表达比的分析显示，在乳腺、淋巴、皮肤和肝脏的正常组织和癌组织中存在显著差异，这表明这两种TMEM蛋白都可能成为某些人类癌症的潜在有用标记物。
Transmembrane (TMEM)-176A and 176B proteins belong to the MS4A family of proteins whose function in the immune system remains unclear. TMEM176A transcripts were previously shown to be elevated in liver cancer or kidney tissue with proteinuria, while marked changes in TMEM176B transcripts have been found in tolerated tissue allografts and neoplastic fibroblasts. To study the functional relationship between human TMEM176A and 176B and their putative link to cancer, we used polymerase chain reaction and biochemical assays. Here, we show that TMEM176A and 176B are widely expressed in all human tissues examined. Co-immunoprecipitation of heterologously expressed TMEM176A and 176B revealed direct physical interaction. To determine the relevance of such interaction to cancer pathology, we analyzed biopsied tissue samples from a variety of normal and cancer tissues. Our data reveal that human TMEM176A and 176B protein levels are significantly elevated in lymphoma, but not in normal tissues. The protein levels of TMEM176A are also significantly increased in lung carcinoma. Finally, analysis of the protein expression ratio of TMEM176A over 176B showed significant differences between normal and cancer tissues of the breast, lymph, skin, and liver, which indicates that both TMEM proteins could be potential useful markers for certain human cancers.