Blesch A, Bosserhoff A K, Apfel R, Behl C, Hessdoerfer B, Schmitt A, Jachimczak P, Lottspeich F, Buettner R, Bogdahn U
Department of Neurology, University of Würzburg, Federal Republic of Germany.
Cancer Res. 1994 Nov 1;54(21):5695-701.
Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization. MIA is translated as a 131-amino acid precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal. A murine complementary DNA was isolated that encoded a MIA-protein with 88% amino acid identity. MIA is secreted into the culture supernatant by several malignant melanoma cell lines as an M(r) 11,000 autocrine growth factor and acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas. MIA has no homology to any other known protein and, therefore, represents a novel type of growth-regulatory factor. Furthermore, we describe a molecular approach to express functionally active MIA in Escherichia coli, which might be attractive as a future antitumor therapeutical substance.
恶性黑色素瘤细胞的生长和进展受到肿瘤细胞与局部环境所产生的复杂的生长刺激和抑制因子网络的影响。在此，我们报告一种新型生长调节蛋白的纯化及分子克隆，该蛋白命名为黑色素瘤抑制活性蛋白（MIA），并提供其初步功能特征。MIA最初被翻译为131个氨基酸的前体，在假定的分泌信号被切割后加工成成熟的107个氨基酸的蛋白质。分离出一种小鼠互补DNA，其编码的MIA蛋白具有88%的氨基酸同源性。MIA作为一种相对分子质量为11,000的自分泌生长因子被几种恶性黑色素瘤细胞系分泌到培养上清液中，并作为一种有效的肿瘤细胞生长抑制剂作用于恶性黑色素瘤细胞和其他一些神经外胚层肿瘤，包括神经胶质瘤。MIA与任何其他已知蛋白均无同源性，因此代表一种新型的生长调节因子。此外，我们描述了一种在大肠杆菌中表达具有功能活性的MIA的分子方法，这作为一种未来的抗肿瘤治疗物质可能具有吸引力。
