Frisch S M
La Jolla Cancer Research Foundation, La Jolla, California 92037.
J Cell Biol. 1994 Nov;127(4):1085-96. doi: 10.1083/jcb.127.4.1085.
Cells closely resembling epithelia constitute the first specific cell type in a mammalian embryo. Many other cell types emerge via epithelial-mesenchymal differentiation. The transcription factors and signal transduction pathways involved in this differentiation are being elucidated. I have previously reported (Frisch, 1991) that adenovirus E1a is a tumor suppressor gene in certain human cell lines. In the present report, I demonstrate that E1a expression caused diverse human tumor cells (rhabdomyosarcoma, fibrosarcoma, melanoma, osteosarcoma) and fibroblasts to assume at least two of the following epithelial characteristics: (a) epithelioid morphology; (b) epithelial-type intercellular adhesion proteins localized to newly formed junctional complexes; (c) keratin-containing intermediate filaments; and (d) down-regulation of non-epithelial genes. E1a thus appeared to partially convert diverse human tumor cells into an epithelial phenotype. This provides a new system for molecular analysis of epithelial-mesenchymal interconversions. This effect may also contribute to E1a's tumor suppression activity, possibly through sensitization to anoikis (Frisch, S.M., and H. Francis, 1994. J. Cell Biol. 124:619-626).
与上皮细胞极为相似的细胞构成了哺乳动物胚胎中的第一种特定细胞类型。许多其他细胞类型通过上皮-间充质分化产生。参与这种分化的转录因子和信号转导途径正在被阐明。我之前曾报道过（弗里施，1991年），腺病毒E1a在某些人类细胞系中是一种肿瘤抑制基因。在本报告中，我证明E1a的表达使多种人类肿瘤细胞（横纹肌肉瘤、纤维肉瘤、黑色素瘤、骨肉瘤）和成纤维细胞呈现出以下至少两种上皮特征：（a）上皮样形态；（b）定位于新形成的连接复合体的上皮型细胞间粘附蛋白；（c）含角蛋白的中间丝；以及（d）非上皮基因的下调。因此，E1a似乎能将多种人类肿瘤细胞部分转化为上皮表型。这为上皮-间充质相互转化的分子分析提供了一个新系统。这种效应也可能有助于E1a的肿瘤抑制活性，可能是通过对失巢凋亡的敏感性（弗里施，S.M.，和H.弗朗西斯，1994年。《细胞生物学杂志》124:619 - 626）。
