Treston A M, Scott F M, Vos M, Iwai N, Mains R E, Eipper B A, Cuttitta F, Mulshine J L
Intervention Section, National Cancer Institute Division of Cancer Prevention and Control, Rockville, Maryland 20850.
Cell Growth Differ. 1993 Nov;4(11):911-20.
Peptide alpha-amidation is a posttranslational modification of approximately half of all endocrine and neuroendocrine peptide hormones, including several hormones with mitogenic effects for tumor cells, and is typically essential for complete hormonal bioactivity. alpha-Amidated peptide hormones have been reported to be autocrine growth factors for small cell lung cancer cells. We report here that a variety of human lung tumor cell lines express both enzymes required for the two-step conversion of inactive glycine-extended peptides into their active COOH-terminal alpha-amide analogues. Human tumor cell peptidylglycine alpha-amidation enzymes are present in multiple molecular forms. Both proteins are metalloenzymes which are present at highest concentrations in secretory granules in neuroendocrine cell lines. The expression of these enzymes is positively correlated with expression of other markers of the neuroendocrine phenotype, such as DOPA decarboxylase. Peptidylglycine alpha-amidating enzyme-specific activities are approximately 50-fold higher in extracts of endocrine cell lines (lung small cell and carcinoid) than of nonendocrine lines. Biochemical characterization of the peptidylglycine alpha-amidating enzymes will enable development of tools for detection of endocrine processes in the early stages of neoplasia and for interruption of autocrine stimulation pathways in tumor cells.
肽α-酰胺化是大约一半的内分泌和神经内分泌肽激素的翻译后修饰，包括几种对肿瘤细胞有促有丝分裂作用的激素，并且通常对于完整的激素生物活性至关重要。据报道，α-酰胺化肽激素是小细胞肺癌细胞的自分泌生长因子。我们在此报告，多种人类肺癌细胞系表达将无活性的甘氨酸延伸肽两步转化为其活性COOH末端α-酰胺类似物所需的两种酶。人类肿瘤细胞肽基甘氨酸α-酰胺化酶以多种分子形式存在。这两种蛋白质都是金属酶，在神经内分泌细胞系的分泌颗粒中浓度最高。这些酶的表达与神经内分泌表型的其他标志物（如多巴脱羧酶）的表达呈正相关。肽基甘氨酸α-酰胺化酶的比活性在内分泌细胞系（肺小细胞和类癌）提取物中比非内分泌细胞系高约50倍。肽基甘氨酸α-酰胺化酶的生化特性将有助于开发用于检测肿瘤形成早期内分泌过程以及中断肿瘤细胞自分泌刺激途径的工具。
