INTERMEDIATE FILAMENTS IN SIMPLE EPITHELIAL CELLS

简单上皮细胞中的中间丝

基本信息

批准号：
2182584
负责人：
KATRINA T TREVOR
金额：
$ 14.78万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-07-01 至 1995-06-30
项目状态：
已结题

项目摘要

The long term objective of this project is to elucidate the role of keratin and vimentin intermediate filaments (IFs) in the differentiation and development of simple epithelium. Although much is known about the gene arrangement, protein sequence and tissue specific expression of IFs, their cellular function remains unclear. The biochemical heterogeneity of the numerously described IF subunits suggests that IFs have functionally diverse roles in different specialized cells. The murine simple epithelial keratins Endo A and Endo B (mouse homologues of the human keratins K8 and K18, respectively) are expressed in all simple epithelia of the adult and are the first IFs expressed in early embryogenesis. Filaments are first observed in the 8-cell embryo and later in trophectoderm and parietal and visceral endoderm. Visceral endoderm cells form a compact, polarized epithelium surrounding the developing embryo and only display IFs composed of Endo A and Endo B while parietal endoderm cells are highly migratory in the developing embryo and appear to coexpress vimentin IFs. Although vimentin expression is normally restricted to cells in vitro and mesenchymal cell types, its expression is also correlated with the metastatic potential of some epithelial neoplasms. Because large numbers of early embryonic cell types are difficult to obtain, the HR9 parietal endoderm cell line and F9 embryonal carcinoma (EC) cells are useful models of early embryonic cell types. F9 Ec cells can be induced to differentiate to visceral or parietal endoderm in monolayer or aggregate cultures. Aggregate differentiation of F9 cells serves as an extremely useful three- dimensional model for visceral endoderm development. As a means of defining the function of keratin and vimentin IFs in these simple epithelial cell types, we propose to examine: 1) the biological and structural effects of IF disruption induced by the expression of mutant Endo Bor vimentin proteins in HR9 cells nad differentiating F9 cultures; 2) the effects of vimentin expression on the phenotype of compact visceral endoderm cells and 3) the molecular and biological aspects of F9 EC cell differentiation in the absence of Endo B protein in cells possessing site- directed mutagenized Endo B alleles. These molecular approaches to study biological behavior will enhance our understanding of simple epithelial cell structure and morphogenesis, early embryonic development, and potentially the metastatic phenotype of transformed epithelial cells.

该项目的长期目标是阐明角蛋白的作用和波形蛋白中间丝（IFS）开发简单的上皮。虽然对基因知之甚少 IFS的排列，蛋白质序列和组织特异性表达细胞功能尚不清楚。生化异质性如果亚基表明IF具有功能上的ifs，多大描述在不同的专用细胞中的各种作用。鼠简单的上皮角蛋白Endo A和Endo B（人角蛋白K8的小鼠同源物和 K18分别在成年人的所有简单上皮中表达）是早期胚胎发生中的第一个IF。细丝是第一在8细胞胚胎中观察到，然后在滋养外胚层和顶叶中观察到内脏内胚层。内脏内胚层细胞形成一个紧凑的极化发育中的胚胎周围的上皮，仅显示组成 eNDO A和ENDO B的范围内胚层细胞在高度迁移发育中的胚胎并似乎可以共表达波形蛋白IF。虽然波形蛋白表达通常仅限于体外细胞，并且间充质细胞类型，其表达也与某些上皮肿瘤的转移潜力。因为大量早期的胚胎细胞类型很难获得HR9顶叶内胚层细胞系和F9胚胎癌（EC）细胞是有用的模型早期胚胎细胞类型。 F9 EC细胞可以诱导以区分在单层或骨料培养物中内脏或顶叶内胚层。 F9细胞的骨料分化是一种极为有用的三内脏内胚层开发的维度模型。作为一种在这些简单的上皮细胞类型，我们建议检查：1）生物学和突变体表达引起的IF造成的结构效应 HR9细胞中的胚胎波形蛋白蛋白NAD区分F9培养物； 2）波形蛋白表达对紧凑型内脏表型的影响内胚细胞和3）F9 EC细胞的分子和生物学方面在缺乏含有位点的细胞中的依托B蛋白的情况下分化定向诱变的内托等位基因。这些研究生物学行为的分子方法将增强我们的了解简单的上皮细胞结构和形态发生，早期胚胎发育，可能是转移表型转化的上皮细胞。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Chromosomal aberrations in two sporadic gastrinomas.

两种散发性胃泌素瘤的染色体畸变。

DOI：
10.1016/0165-4608(93)90042-k
发表时间：
1993
期刊：
Cancer genetics and cytogenetics
影响因子：
0
作者：
Herrmann,ME;Rydstedt,LL;Talpos,GB;Trevor,KT;Wolman,SR;Mohamed,AN;Ratner,S;Lalley,PA
通讯作者：
Lalley,PA

Association of vimentin intermediate filaments with the centrosome.

波形蛋白中间丝与中心体的关联。