Zhou G H, Sechrist G L, Brattain M G, Mulder K M
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
J Cell Physiol. 1995 Dec;165(3):512-20. doi: 10.1002/jcp.1041650309.
Spontaneously arising, TGF beta 1-resistant colonies were isolated directly from the soft agarose plates of MOSER human colon carcinoma cells grown in the presence of TGF beta 1 but in the absence of serum. The colonies were cloned by limiting dilution and screened in a monolayer proliferation assay for sensitivity to TGF beta 1 and TGF beta 2 isoforms. Cell clones selectively sensitive or resistant to these isoforms in the growth inhibition assay displayed similar differential sensitivities to TGF beta isoforms for production of the extracellular matrix proteins laminin and fibronectin, as well as for the expression of the colon cell differentiation marker carcinoembryonic antigen. Differential receptor binding profiles for TGF beta 1 and TGF beta 2 were observed among the clones. The isolation of cell clones selectively resistant or sensitive to TGF beta isoforms as well as the identification of differential receptor binding profiles among the clones indicate the heterogeneity of TGF beta responsiveness that exists naturally in human colon tumor cells and stress the importance of defining mechanisms underlying differential responsiveness to TGF beta isoforms.
从在存在转化生长因子β1（TGFβ1）但无血清条件下培养的MOSER人结肠癌细胞的软琼脂平板中，直接分离出自发产生的对TGFβ1耐药的集落。通过有限稀释法对这些集落进行克隆，并在单层增殖试验中筛选其对TGFβ1和TGFβ2亚型的敏感性。在生长抑制试验中对这些亚型选择性敏感或耐药的细胞克隆，在细胞外基质蛋白层粘连蛋白和纤连蛋白的产生以及结肠细胞分化标志物癌胚抗原的表达方面，对TGFβ亚型表现出相似的差异敏感性。在这些克隆中观察到了TGFβ1和TGFβ2不同的受体结合谱。对TGFβ亚型选择性耐药或敏感的细胞克隆的分离以及克隆间不同受体结合谱的鉴定，表明人结肠肿瘤细胞中天然存在TGFβ反应性的异质性，并强调了确定对TGFβ亚型差异反应性潜在机制的重要性。
