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相关概念视频

The Ras Gene02:38

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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一种不活跃的Braf激酶突变诱导肺腺癌

Patricia Nieto1, Chiara Ambrogio1, Laura Esteban-Burgos1

  • 1Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.

Nature
|August 8, 2017
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概括

不活化的BRAF突变通过改变MAPK信号来启动肺腺癌. 野生型BRAF对瘤生长至关重要,

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科学领域:

  • 癌症学
  • 分子生物学
  • 癌症遗传学

背景情况:

  • 肺腺癌的发病因子往往是未知的,阻碍了向治疗的发展.
  • 与其他癌症中常见的激活突变不同,非激活的BRAF突变在肺癌中普遍存在.

研究的目的:

  • 研究BRAF失活突变在肺癌发生过程中的作用.
  • 探索BRAF,KRAS和MAPK信号在肺腺癌发育和进展中的相互作用.

主要方法:

  • 在体内表达不活性Braf (D631A) 和Kras (G12V) 突变的小鼠模型.
  • 对瘤发病,进展和细胞类型分化的分析.
  • 药理上抑制MEK (Mek) 来调节MAPK的信号传递.

主要成果:

  • 在小鼠中,表达非活性激酶Braf (D631A) 引发肺腺癌.
  • 克拉斯 (G12V) 和布拉夫 (D631A) 的同时表达通过克拉夫激酶加速了瘤的启动和进展.
  • 野生型Braf的切除会增加MAPK信号和瘤毒性,但也会诱导球状细胞转基因分化和致死性病变.

结论:

  • 在肺癌中,BRAF 失活突变是引发事件的原因.
  • MAPK通路的信号强度决定了瘤的表型和细胞起源.
  • 针对BRAF和了解MAPK通路动态对于肺腺癌治疗至关重要.