Expression of Smad4 in the FaDu cell line partially restores TGF-beta growth inhibition but is not sufficient to regulate fibronectin expression or suppress tumorigenicity.

Hummer BT; Bartlett C; Henry EWeissman BE

首页> 外文期刊>Journal of Cellular Physiology >Expression of Smad4 in the FaDu cell line partially restores TGF-beta growth inhibition but is not sufficient to regulate fibronectin expression or suppress tumorigenicity.

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Expression of Smad4 in the FaDu cell line partially restores TGF-beta growth inhibition but is not sufficient to regulate fibronectin expression or suppress tumorigenicity.

机译：表达式FaDu Smad4的细胞系部分恢复及增长抑制但不足以调节纤连蛋白吗表达式或抑制致瘤性。

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Mutations of the Smad4 gene, a member of a group of TGF-beta signal transduction components, occur in several types of cancer suggesting that its inactivation significantly affects TGF-beta responsiveness in these tumors. To further investigate the role of Smad4 with respect to TGF-beta signaling and carcinogenesis, we re-expressed the Smad4 gene in the Smad4-deficient cancer cell line FaDu by microcell-mediated chromosome transfer (MMCT) and retroviral infection to closely approximate physiological protein levels. The Smad4-expressing FaDu clones were then evaluated for TGF-beta responsiveness to assess the role of Smad4 in TGF-beta-induced growth inhibition and target gene regulation. We found that the re-expression of the Smad4 gene by either method partially restored TGF-beta responsiveness in FaDu cells with respect to both growth inhibition and expression of p21WAF1/CIP1 and p15INK4B. However, only the microcell hybrids showed growth retardation in organotypic raft culture and an enhanced abilityto upregulate fibronectin. In contrast, the re-expression of Smad4 by either method failed to suppress tumorigenicity. These results suggest that in addition to a homozygous deletion of Smad4, FaDu cells contain additional defects within the TGF-beta signaling pathway, thereby limiting the extent of TGF-beta responsiveness upon Smad4 re-expression and perhaps accounting for the inability to induce p15INK4B to a high level. They also demonstrate the advantages of providing a physiological extracellular environment, when assessing TGFbeta responsiveness.

机译：Smad4的突变基因,一组的成员及信号转导组件,发生在暗示它的几种类型的癌症失活显著影响及护这些肿瘤的反应。Smad4的作用对进行调查及信号和致癌作用,我们重新Smad4基因Smad4-deficient FaDu癌症细胞系microcell-mediated染色体(MMCT)和转移逆转录病毒感染密切近似生理上的蛋白质含量。Smad4-expressing FaDu克隆被评估为鉴定及响应能力评估的作用在TGF-beta-induced生长抑制和Smad4目标基因调控。Smad4基因的表达,通过方法部分恢复及响应能力FaDu细胞对生长抑制p21WAF1 / CIP1表达和p15INK4B。然而,只有微细胞混合动力车显示增长缺陷在organotypic筏文化和一个增强能力移植纤连蛋白。相反,Smad4的表达方法未能抑制致瘤性。结果表明,除了纯合子删除Smad4, FaDu细胞包含额外的及信号通路中的缺陷,从而限制及的程度对Smad4的表达和响应能力也许占不能诱导p15INK4B到一个很高的水平。提供生理上的优势细胞外环境,评估TGFbeta时响应性。

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来源
《Journal of Cellular Physiology》 |2003年第3期|289-302|共14页
作者
Hummer BT; Bartlett C; Henry EWeissman BE;
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Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA. bhummer@som.umaryland.edu;

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正文语种英语
中图分类细胞生物学;
关键词
Fibronectins; Trans-Activators; Transforming Growth Factor betaGrowth Retardationgrowth inhibitionmicrocell hybridsTumorigenicityCDKN2B geneResponsivenessSMAD4 geneDNA-Binding ProteinsGrowth InhibitorsFaDu cell line;

机译：纤连蛋白;Trans-Activators;将增长因素betaGrowth Retardationgrowthinhibitionmicrocell hybridsTumorigenicityCDKN2BgeneResponsivenessSMAD4 geneDNA-BindingProteinsGrowth InhibitorsFaDu细胞系;

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Expression of Smad4 in the FaDu cell line partially restores TGF-beta growth inhibition but is not sufficient to regulate fibronectin expression or suppress tumorigenicity.

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