Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice

Pheochromocytoma cell lines from heterozygous neurofibromatosis knockout mice
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DOI:
10.1007/s004410000290
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发表时间:
2000-12-01
影响因子:
3.6
通讯作者:
Tischler, AS
Tischler, AS
中科院分区:
生物学3区
文献类型:
--
作者:
Powers, JF;Evinger, MJ;Tischler, AS

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神经纤维瘤病基因Nf1杂合敲除突变小鼠的嗜铬细胞瘤已发展成可移植的肿瘤和细胞系。Nf1编码ms- gtpase激活蛋白,神经纤维蛋白,小鼠嗜铬细胞瘤(MPC)细胞在原代培养中通常表现出广泛的自发神经元分化,这可能是由于剩余野生型等位基因的丢失和ras信号调节缺陷造成的。然而,所有MPC细胞系都表达神经纤维蛋白,这表明保存野生型等位基因可能需要允许MPC细胞在体外繁殖。MPC细胞系与PC12细胞的不同之处在于它们既表达内源性苯乙醇胺n -甲基转移酶(PNMT),也表达全长PNMT报告基因。在悬浮培养中,通过地塞米松和细胞间接触可增加PNMT的表达。小鼠嗜铬细胞瘤是研究肾上腺髓质肿瘤细胞生长和分化调控基因和信号通路的新工具,也是研究PNMT表达调控的独特模型。
Transplantable tumors and cell lines have been developed from pheochromocytomas arising in mice with a heterozygous knockout mutation of the neurofibromatosis gene, Nf1. Nf1 encodes a ms-GTPase-activating protein, neurofibromin, and mouse pheochromocytoma (MPC) cells in primary cultures typically show extensive spontaneous neuronal differentiation that may result from the loss of the remaining wild-type allele and defective regulation of ras signaling. However, all MPC cell lines express neurofibromin, suggesting that preservation of the wild-type allele may be required to permit the propagation of MPC cells in vitro. MPC lines differ from PC12 cells in that they express both endogenous phenylethanolamine N-methyltransferase (PNMT) and full-length PNMT reporter constructs. PNMT expression is increased by dexamethasone and by cell-cell contact in suspension cultures. Mouse pheochromocytomas are a new tool for studying genes and signaling pathways that regulate cell growth and differentiation in adrenal medullary neoplasms and are a unique model for studying the regulation of PNMT expression.