Zhou G H, Sechrist G L, Periyasamy S, Brattain M G, Mulder K M
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Cancer Res. 1995 May 15;55(10):2056-62.
Here we describe human colon carcinoma cell clones, isolated from a transforming growth factor beta (TGF-beta)-responsive parental cell line, which display differential sensitivities to TGF-beta 1 and TGF-beta 2 isoforms. In a monolayer proliferation assay, some clones were sensitive to both isoforms (IC50 = 0.1-0.6 ng/ml; S1S2) while others were resistant to both isoforms (IC50 > 5 ng/ml; R1R2). Still other clones (R1S2) were sensitive to TGF-beta 2 (IC50 = 0.1-0.2 ng/ml), but were resistant to TGF-beta 1 (IC50 > or = 5 ng/ml). In S1S2 cells, both TGF-beta isoforms resulted in a repression of c-myc mRNA expression, a concentration-dependent increase in fibronectin levels, and an enhanced production of the colon cell differentiation marker carcinoembryonic antigen. In contrast, R1R2 cells did not display these responses, or did so only to a limited extent. In R1S2 cells, TGF-beta 2 elicited these responses, yet TGF-beta 1 was essentially without effect. Receptor cross-linking experiments indicated that TGF-beta resistance in this model system was not generally associated with a complete lack of expression of either type I or II receptors. Moreover, the R1S2 type clones were heterogeneous, although the majority of them displayed binding to type I receptors by TGF-beta 2 but not by TGF-beta 1. These data suggest that either the TGF-beta 1 and TGF-beta 2 isoforms differ with respect to their ability to interact with the type I and II classes of receptors, or the TGF-beta 1 and TGF-beta 2 isoforms can interact with distinct receptor proteins of the type I and II classes in this model system.
在此，我们描述了从对转化生长因子β（TGF-β）有反应的亲代细胞系中分离出的人结肠癌细胞克隆，这些克隆对TGF-β1和TGF-β2亚型表现出不同的敏感性。在单层增殖试验中，一些克隆对两种亚型均敏感（IC50 = 0.1 - 0.6 ng/ml；S1S2），而另一些克隆对两种亚型均耐药（IC50 > 5 ng/ml；R1R2）。还有一些克隆（R1S2）对TGF-β2敏感（IC50 = 0.1 - 0.2 ng/ml），但对TGF-β1耐药（IC50 ≥ 5 ng/ml）。在S1S2细胞中，两种TGF-β亚型均导致c-myc mRNA表达受到抑制，纤连蛋白水平呈浓度依赖性增加，以及结肠细胞分化标志物癌胚抗原的产生增加。相比之下，R1R2细胞未表现出这些反应，或仅在有限程度上表现出这些反应。在R1S2细胞中，TGF-β2引发了这些反应，但TGF-β1基本无作用。受体交联实验表明，该模型系统中的TGF-β耐药性通常与I型或II型受体的完全缺失表达无关。此外，R1S2型克隆具有异质性，尽管它们中的大多数显示出能与TGF-β2结合I型受体，但不能与TGF-β1结合。这些数据表明，要么TGF-β1和TGF-β2亚型在与I型和II型受体相互作用的能力方面存在差异，要么在该模型系统中，TGF-β1和TGF-β2亚型可以与I型和II型受体的不同受体蛋白相互作用。
