Expression of T-cadherin (CDH13, H-cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells
Expression of T-cadherin (CDH13, H-cadherin) in human brain and its characteristics as a negative growth regulator of epidermal growth factor in neuroblastoma cells
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DOI：
10.1046/j.1471-4159.2000.0741489.x
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发表时间：
2000-04-01
影响因子：
4.7
通讯作者：
Ohtsuki, Y
中科院分区：
文献类型：
--
作者：
Takeuchi, T;Misaki, A;Ohtsuki, Y
在本研究中，我们首先研究了T-钙粘蛋白的表达在人类中枢神经系统的北方印迹分析，免疫组织化学染色，原位杂交。北方印迹分析表明，在成人大脑皮质，髓质，丘脑和中脑表达的T-钙粘蛋白。免疫组织化学染色与新产生的单克隆抗体，指定MA-511，揭示了强烈的表达T-cadherin的神经细胞表面膜和神经突在成人大脑皮质，延髓，橄榄核。T-cadherin在脊髓中几乎不表达。我们进一步研究了T-cadherin在各种发育中的神经系统中的表达，发现T-cadherin在发育中的脑中的表达低于成人脑。原位杂交显示，延髓和橄榄核的神经细胞，而不是在脊髓，具有T-钙粘蛋白分子。我们用含T-cadherin cDNA的表达载体转染T-cadherin阴性的TGW和NH-12神经母细胞瘤细胞。表达T-钙粘蛋白的神经母细胞瘤细胞对表皮生长因子失去促有丝分裂增殖反应。已知表皮生长因子是神经干细胞增殖所必需的。这一发现，与本研究的结果一起，表明T-钙粘蛋白作为神经细胞生长的负调控因子发挥作用。
In the present study, we first examined the expression of T-cadherin in human CNS by northern blot analysis, immunohistochemical staining, and in situ hybridization. Northern blot analysis demonstrated expression of T-cadherin in human adult cerebral cortex, medulla, thalamus, and midbrain. Immunohistochemical staining with a newly generated monoclonal antibody, designated MA-511, revealed strong expression of T-cadherin in neural cell surface membrane and neurites in adult cerebral cortex, medulla oblongata, and nucleus olivaris. Little or no expression of T-cadherin was found in spinal cord. We further examined T-cadherin expression in various developing nervous systems, and found that T-cadherin expression was lower in developing brain than in adult brain. In situ hybridization revealed that neural cells in medulla oblongata and nucleus olivaris, but not in spinal cord, possessed T-cadherin molecules. We transfected T-cadherin-negative TGW and NH-12 neuroblastoma cells with a T-cadherin cDNA-containing expression vector. T-cadherin-expressing neuroblastoma cells lost mitogenic proliferative response to epidermal growth factor. Epidermal growth factor is known to be required for proliferation of neural stem cells. This finding, together with those of the present study, suggests that T-cadherin functions as a negative regulator of neural cell growth.