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鼠 Mageb18 基因编码一种广泛表达的 I 型 MAGE 蛋白,调节黑色素瘤 B16-F0 细胞的增殖和凋亡。

The mouse Mageb18 gene encodes a ubiquitously expressed type I MAGE protein and regulates cell proliferation and apoptosis in melanoma B16-F0 cells.

机构信息

The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, People's Republic of China.

出版信息

Biochem J. 2012 May 1;443(3):779-88. doi: 10.1042/BJ20112054.

Abstract

Although many cancer vaccines have been developed against type I MAGE (melanoma antigen) genes owing to their shared tumour-specific expression properties, studies about their expression and functions are relatively limited. In the present study, we first identify a non-testis-specific type I MAGE gene, Mageb18 (melanoma antigen family B 18). Mouse Mageb18 is also expressed in digestion- and immune-related tissues as well as testis, and its expression in testis is age-dependent. Mageb18 is expressed in many mouse-derived cell lines, and DNA demethylation and histone acetylation mediate the reactivation of Mageb18 in Mageb18-negtive H22 and C6 cells. We also show that mouse Mageb18 encodes a 46 kDa protein which is predominantly localized in the cytoplasm. In testis, the endogenous MAGEB18 protein is mainly expressed in proliferative spermatogonia and primary and secondary spermatocytes, but less so in spermatids. Finally, we demonstrate that knockdown of MAGEB18 inhibits the growth of B16-F0 cells and induces apoptosis, which correlates with increased levels of TP53 (tumour protein 53), p21, Bax and caspase 3. The results of the present study thus uncover an important phenomenon that the expression of certain type I MAGE genes, at least for Mageb18, is non-testis-specific. Although they can regulate various malignant phenotypes of cancer cells, it is necessary to study further their expression pattern in normal tissues before using them to develop more effective and safer cancer vaccines.

摘要

尽管已经针对 I 型 MAGE(黑色素瘤抗原)基因开发了许多癌症疫苗,因为它们具有共享的肿瘤特异性表达特性,但对其表达和功能的研究相对有限。在本研究中,我们首先鉴定了一种非睾丸特异性的 I 型 MAGE 基因 Mageb18(黑色素瘤抗原家族 B18)。小鼠 Mageb18 也在消化和免疫相关组织以及睾丸中表达,其在睾丸中的表达具有年龄依赖性。Mageb18 在许多源自小鼠的细胞系中表达,DNA 去甲基化和组蛋白乙酰化介导 Mageb18 在 Mageb18 阴性的 H22 和 C6 细胞中的重新激活。我们还表明,小鼠 Mageb18 编码一种 46 kDa 的蛋白质,主要定位于细胞质中。在睾丸中,内源性 MAGEB18 蛋白主要表达于增殖性精原细胞和初级和次级精母细胞中,但在精细胞中表达较少。最后,我们证明下调 MAGEB18 抑制了 B16-F0 细胞的生长并诱导了细胞凋亡,这与 TP53(肿瘤蛋白 53)、p21、Bax 和 caspase 3 水平的增加相关。因此,本研究的结果揭示了一个重要现象,即某些 I 型 MAGE 基因的表达,至少对于 Mageb18 而言,是非睾丸特异性的。尽管它们可以调节癌细胞的各种恶性表型,但在将它们用于开发更有效和更安全的癌症疫苗之前,有必要进一步研究它们在正常组织中的表达模式。

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