Department of Biological Science and Center for Applied Biotechnology Studies, California State University Fullerton, Fullerton, CA 92831, USA.
Acta Histochem. 2012 Nov;114(7):705-12. doi: 10.1016/j.acthis.2011.12.006. Epub 2012 Jan 12.
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.
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。先前的研究表明，TMEM176A 转录本在肝癌或蛋白尿肾组织中升高，而 TMEM176B 转录本在耐受组织同种异体移植物和肿瘤成纤维细胞中发生明显变化。为了研究人 TMEM176A 和 176B 之间的功能关系及其与癌症的潜在联系，我们使用聚合酶链反应和生化测定法。在这里，我们表明 TMEM176A 和 176B 在所有检查的人类组织中广泛表达。异源表达的 TMEM176A 和 176B 的共免疫沉淀显示直接的物理相互作用。为了确定这种相互作用与癌症病理学的相关性，我们分析了来自各种正常和癌症组织的活检组织样本。我们的数据表明，人 TMEM176A 和 176B 蛋白水平在淋巴瘤中显著升高，但在正常组织中没有升高。TMEM176A 的蛋白水平在肺癌中也显著增加。最后，分析 TMEM176A 与 176B 的蛋白表达比率表明，乳腺癌、淋巴结、皮肤和肝脏的正常组织和癌症组织之间存在显著差异，这表明这两种 TMEM 蛋白都可能是某些人类癌症的潜在有用标志物。
