随着表皮瘤发生的反应,带有p53损失的 stromal mesenchyme 的选择性进化
Reginald Hill1, Yurong Song, Robert D Cardiff
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
癌症的进展不仅仅涉及瘤细胞. 表皮应激可以在瘤微环境中非自主选择纤维细胞突变,特别是p53损失.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境研究 研究
背景情况:
- 传统上,对癌症的理解主要集中在瘤细胞异常上.
- 瘤微环境,包括纤维细胞,显著影响瘤发生.
- 证据表明,在瘤进展过程中, stromal 细胞中发生的遗传/表观遗传变化的非自主选择.
研究的目的:
- 通过实验评估纤维细胞是否因上皮质的瘤性压力而经历遗传/表观遗传变化.
- 为了研究细胞间通信在癌症发育过程中驱动树皮细胞异常的作用.
主要方法:
- 利用前列腺癌的小鼠模型.
- 通过抑制prb功能的诱导上皮细胞循环中断.
- 分析了相关纤维细胞中的膜信号响应.
- 在选择性压力下评估纤维细胞增殖和p53状态.
主要成果:
- 表皮细胞循环中断触发了纤维细胞中的膜p53反应.
- 这种膜信号抑制了正常的纤维细胞增殖.
- 强大的选择性压力被施加在石头上.
- 由此产生的间酶体表现出高增殖率和获得的p53损失.
结论:
- 瘤微环境中的细胞间通信驱动着非自主选择的 stromal 异常.
- 表皮中的瘤性压力可以导致纤维细胞中瘤抑制基因损失 (p53) 的选择.
- 这种机制通过改变纤维细胞区间来促进瘤的进展.
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