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

IA-2及其类似物IA-2β是1型糖尿病发病的重要因素。妊娠和月经周期与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，而且在秀丽隐杆线虫和斑马鱼中也保存和拥有，所以它们被认为是所有动物物种的重要蛋白质。然而，它们的功能尚未得到很好的澄清。由于IA-2和IA-2β在犬中肯定是保守的，因此我们在本研究中确认它们是否是犬的良好内分泌肿瘤标志物。它们的生化和形态学特征在正常和内分泌肿瘤荷瘤犬进行检查，使用荧光化学和蛋白质印迹。在正常犬脑组织化学中，IA-2和IA-2β以细颗粒形式定位于脑神经小层、腺垂体、甲状腺C细胞、肠嗜铬细胞、胰岛细胞和肾上腺嗜铬细胞的突触细胞间隙中。在荷瘤犬的垂体腺瘤、髓样癌、胃类癌和胰腺胰岛素瘤中均可检测到。免疫组化结果显示，IA-2β的免疫反应性均强于IA-2。免疫印迹法检测到IA-2和IA-2β在大脑、垂体、胰腺和肾上腺的突触、核和微粒体组分中的特异性条带。在半定量分析中，IA-2β的表达均大于IA-2。虽然这两种蛋白质都被认为是犬和人神经内分泌系统中非常重要的因子，但IA-2β在犬中的作用可能比IA-2更重要。提示IA-2β可能是犬内分泌肿瘤的免疫组化肿瘤标志物。

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.