Possibility as a tumor marker on IA-2 for dogs.

IA-2及其类似物IA-2β是发生1型糖尿病的重要因素。它们还与妊娠和月经周期的神经内分泌系统有关。由于它们不仅在哺乳动物中保存和拥有，而且在秀丽隐杆线虫和斑马鱼中也存在，因此人们认为它们是所有动物物种的关键蛋白质。然而，它们的功能尚未得到很好的阐明。由于IA-2和IA-2β在犬体内具有一定的保守性，我们在本研究中确认它们是否可以作为犬良好的内分泌肿瘤标志物。用免疫组织化学和免疫印迹法检测正常和内分泌荷瘤犬的生化和形态学特征。在正常犬的免疫组织化学中，IA-2和IA-2β以细小颗粒的形式存在于脑神经细胞、腺垂体、甲状腺C细胞、肠色素细胞、胰岛细胞和肾上腺色素细胞的突触细胞质中。在荷瘤犬的免疫组化中，垂体腺瘤、髓样癌、胃类癌和胰腺胰岛素瘤均可见。对IA-2β的免疫反应均强于对IA-2的免疫反应。在western blotting中，可以在大脑、垂体、胰腺和肾上腺的突触、核和微粒体中检测到IA-2和IA-2β的特异性条带。在半定量分析中，IA-2β的表达量均大于IA-2。虽然这两种蛋白都被认为是狗和人神经内分泌系统的重要因子，但IA-2β在狗体内的作用可能比IA-2更重要。由此可见，IA-2β可能是犬内分泌肿瘤的免疫组织化学标志物，而非IA-2。

IA-2 and its analog, IA-2β, are important factors occurring type 1 diabetes. They also associated with neural endocrine system for pregnancy and menstrual cycle. Because they conserve and possess not only in mammalians, but also in C.elegans and zebra fish, it is supposed that they are crucial proteins for all of animal species. However, functions of them have not been well clarified. Since IA-2 and IA-2β are sure to be conserved in dogs, we confirmed if they would be good endocrine tumor marker for dogs in this research. Their biochemical and morphological characteristics in normal and endocrine tumor-bearing dogs are examined using immunohistochemistries and western blotting. In immunohistochemistries of normal dogs, IA-2 and IA-2β were localized as fine granules in cytoplasms of synapses of the cerebral neuropils, adenohypophyses, C cells of the thyroids, enterochromaffin cells, islet cells of the pancreases, and adrenal chromaffin cells. In immunohistochemistries of tumor-bearing dogs, they could be detected from pituitary adenoma, medullary carcinoma, gastric carcinoid, and pancreatic insulinoma. All the immunoreactivities to IA-2β were stronger than those to IA-2. In western blotting, specific bands to IA-2 and IA-2β could be detected from synapse, nuclear and microsome fractions of the cerebrums, pituitaries, pancreases, and adrenals. In semi-quantitative analyses, all the expressions of IA-2β were greater than those of IA-2. Although both proteins are considered as very important factors of neuroendcrine system in dog, as well as human, IA-2β may play more important roles than IA-2 in dogs. According to these results, IA-2β rather than IA-2 would implicate to be an immunohistochemical tumor marker of canine endocrine tumor.