A human pituitary tumor-derived folliculostellate cell line

A human pituitary tumor-derived folliculostellate cell line
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DOI:
10.1210/jc.85.3.1180
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发表时间:
2000-03-01
影响因子:
5.8
通讯作者:
Klibanski, A
Klibanski, A
中科院分区:
医学2区
文献类型:
--
作者:
Danila, DC;Zhang, X;Klibanski, A

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垂体细胞已被用于研究激素的合成、分泌和调节。然而,缺乏垂体来源的人类细胞系使得在人类中进行此类研究非常困难。激活素是转化生长因子-β细胞因子家族的成员,由垂体分泌,除了调节激素生物合成外,还作为细胞生长和分化的调节剂。在人类垂体中,滤泡星状细胞分泌一种激活素结合和中和蛋白,卵泡抑素。然而,这些细胞在激活素的自分泌/旁分泌调节机制中的作用知之甚少。我们描述了一个人垂体源性滤泡星状细胞系,命名为PDFS,这是从一个临床无功能的垂体大腺瘤自发发展。PDFS细胞呈上皮样形态,胞质突起较长。电子显微镜显示频繁的细胞间连接,包括桥粒,和细胞遗传学分析显示染色体异常的克隆特征。这些细胞表达波形蛋白和神经组织特异性5-100蛋白,这些蛋白是垂体前叶中滤泡星状细胞的特异性标志物,但不表达分泌型垂体细胞标志物。PDFS细胞在锚定非依赖性转化测定中形成大集落。它们表达卵泡抑素和激活素A,并具有完整的激活素细胞内信号传导途径,如通过报告基因测定所确定的。因此,该人细胞系为研究垂体滤泡星状细胞内源性产生的因子对细胞生长和细胞因子产生的调节提供了有用的模型。
Pituitary cells have been used for the study of hormone synthesis, secretion, and regulation. However, the lack of human cell lines of pituitary origin has made such studies in humans very difficult. Activin, a member of the transforming growth factor-beta cytokine family, is secreted by the pituitary and serves, in addition to regulating hormone biosynthesis, as a regulator of cell growth and differentiation. In the human pituitary, folliculo-stellate cells secrete an activin-binding and -neutralizing protein, follistatin. However, the role of these cells in the autocrine/paracrine regulatory mechanisms of activin is poorly understood. We describe a human pituitary-derived folliculostellate cell line, designated PDFS, that was developed spontaneously from a clinically nonfunctioning pituitary macroadenoma. PDFS cells showed an epithelial-like morphology with long cytoplasmic processes. Electron microscopy revealed frequent intercellular junctions, including desmosomes, and cytogenetic analysis showed clonal characteristics with chromosomal abnormalities. These cells express vimentin and the nervous tissue-specific 5-100 protein, specific markers of folliculostellate cells in the anterior pituitary, but no secretory pituitary cell markers. PDFS cells formed large colonies in an anchorage-independent transformation assay. They express follistatin and activin A and have an intact activin intracellular signaling pathway as determined by reporter assays. Therefore, this human cell line provides a useful model for studying the regulation of cell growth and cytokine production by factors endogenously produced in pituitary folliculostellate cells.