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。因为它们不仅在哺乳动物中保存和拥有，而且在线虫和斑马鱼中也存在，因此它们被认为是所有动物物种的关键蛋白质。然而，它们的功能还没有得到很好的阐明。由于IA-2和IA-2β在狗体内肯定是保守的，因此我们在本研究中证实了它们是否可以作为狗的良好内分泌肿瘤标志物。用免疫组织化学和免疫印迹法检测了正常犬和内分泌肿瘤犬的生化和形态特征。在正常犬的免疫组织化学中，IA-2和IA-2β定位于脑神经毛突触、腺垂体、甲状腺C细胞、肠嗜铬细胞、胰腺胰岛细胞和肾上腺嗜铬细胞的胞浆内。在荷瘤犬的免疫组织化学中，可以从垂体腺瘤、髓样癌、胃类癌和胰腺胰岛素瘤中检测到它们。对IA-2β的免疫反应均强于IA-2。免疫印迹法可在大脑、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的表达均高于IA-2。尽管这两种蛋白在犬和人的神经内分泌系统中都被认为是非常重要的因素，但IA-2β在狗的神经内分泌系统中可能比IA-2发挥更重要的作用。根据这些结果，IA-2β而不是IA-2可能是犬内分泌肿瘤的免疫组织化学肿瘤标志物。

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.