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Spheroid Assay to Measure TGF-β-induced Invasion
Published on: November 16, 2011
在癌症中对TGFBR1*6A的体内获取和信号
Boris Pasche1, Thomas J Knobloch, Yansong Bian
1Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine, The Feinberg School of Medicine, Northwestern, University, Chicago, Ill 60611, USA. b-pasche@northwestern.edu
JAMA
|October 6, 2005
概括
常见的TGFBR1*6A多态性是由结直肠癌转移获得的,可能通过改变TGF-β信号来促进瘤生长. 这表明TGFBR1*6A是癌症发展中的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- I型转化生长因子β受体 (TGFBR1) 多态性,TGFBR1*6A,与癌症易感性有关.
- 通过TGFBR1*6A促进癌症发展的确切机制在很大程度上仍未被阐明.
研究的目的:
- 为了研究TGFBR1*6A在原发性瘤和转移中的体质获取.
- 要确定TGFBR1*6A中具有特色的3氨基酸缺失是否是成熟受体或信号序列的一部分.
- 探索TGFBR1*6A信号传递在癌细胞中的功能影响.
主要方法:
- 来自531名癌症患者 (头,结肠直肠,乳腺) 瘤和生殖系组织的分析.
- 在体外转化试验和癌细胞系 (MCF-7,DLD-1,SW48) 稳定转染与TGFBR1*6A变体.
- 评估TGF-β依赖细胞的增殖和TGFBR1*6A的体质获得.
主要成果:
- TGFBR1*6A在29.5%的结直肠癌转移中和较小比例的原发性瘤中被体内获得.
- 对TGFBR1*6A的体质获取与遗传不稳定性标记不相关.
- 成熟的TGFBR1和TGFBR1*6A受体是相同的,信号序列在同一个位置分裂.
- 在癌细胞中,TGFBR1*6A似乎将TGF-β的抑制信号转化为生长刺激信号.
结论:
- 在显著比例的结直肠癌转移中,TGFBR1*6A是通过体质获得的,这赋予了潜在的生长优势.
- 在癌症中,TGFBR1*6A的功能作用似乎是由其信号序列介导的,而不是成熟的受体.
- TGFBR1*6A代表了TGF-β信号在癌症中的新方面,也是潜在的治疗点.
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