Molecular biological study on hormone production and tumor growth in endocrine tumor.

利用分子生物学技术揭示肿瘤生长和激素产生，如高度恶性和低度恶性之间的双向性特征，多种激素在肿瘤中的产生机制，以及功能性和非功能性肿瘤的差异。REG被认为是胰腺腺泡细胞瘤的可靠标记物，但不是内分泌肿瘤的可靠标记物。比较性的。对神经内分泌肉瘤和类癌的研究表明，增殖细胞核抗原阳性的肿瘤细胞在NEC中较高，而在类癌中较低，而在NEG中，HLADR抗原阳性的间质细胞很少，但在类癌中明显。增殖细胞核抗原和人类白细胞抗原-DR抗原似乎都是肿瘤生长的重要因素。II.激素产生：1.经cAMP和佛波酯处理的人神经母细胞瘤细胞株(NB-L)表达多种激素。方法：1.采用原位杂交、免疫细胞化学和放射免疫分析等方法，检测VIP、PHM、神经肽Y、生长抑素、甲硫氨酸脑啡肽和酪氨酸羟化酶(TH)基因。应用原位杂交和免疫组织化学方法检测WDHA综合征节细胞神经母细胞瘤中VIP、PHM、生长抑素、甲硫氨酸脑啡肽、神经肽Y、促肾上腺皮质激素释放肽(CRP)和TH等多种激素基因的表达。对功能性和非功能性嗜铬细胞瘤的儿茶酚胺合成酶进行免疫组织化学检测，发现部分非功能性肾上腺外副神经节瘤缺乏TH.4。对神经内分泌肿瘤中嗜铬粒细胞、突触素和中间丝进行免疫组织化学研究。对神经内分泌肿瘤中芳香族L氨基酸脱羧酶进行了免疫组织化学研究。

This project was focused on revealing I. Tumor growth, and II. Hormone production such as 1)bistological features between highly malignant and low grade malignant tumors, 2)the mechanism of multiple hormone production in the tumors and 3)the differences between functioning and non-functioning tumors using molecular biological techniques.I. Tumor growth :1. Messenger RNA of human regenerating gene(reg)and reg protein were detected in acinar cells of the normal pancreas. Reg was considered to be a : reliable marker for acinar cell tumors of the pancreas, but not for endocrine tumors.2. A comparative. study of neuroendocrine barcinoma(NEC)and carcinoid tumors revealed that frequency of PCNA positive tumor cells are high in NEC but low in carcinoids, and HLA-DR antigen positive stromal cells are few in NEG but evident in carcinoids. Both PCNA and HLA-DR antigen seemed to be important factors on tumor growth.II. Hormone production :1. Human neuroblastoma cell line(NB-l)treated with CAMP and phorbol ester expressed iffultiple hormone. genes such as VIP, PHM, neuropeptide Y, somatostatin, met-enkephalin and tyrosine hydroxylase(TH), using in situ hybridization, imunocytochemistry and radioimmunoassay.2. Ganglioneuroblastomas with WDHA syndrome expressed multiple hormone genes such as VIP, PHM, somatostatin, met-enkephalin, neuropeptide Y, corticotropin releasing peptide(CRP)and TH using in situ hybridization and imunohistochemistry.3. Catecholamine synthesizing enzymes in functioning and non-functioning pheochromocytomas were immunohistochemically examined and it revealed that some of non-functioning extra-adrenal paragangliomas lack TH.4. Immunohistochemical studies of chromogranin, synptophysin and intermediate filaments in neuroendocrine tumors were performed.5. Immunoreactive aromatic L-amino acid decarboxylase in neuroendocrine tumors was investigated.