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  • 基因管理和癌症 -- -- 高级

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    What controls a growing tumor?
    ::什么控制了肿瘤的生长?

    There are two main types of genes involved in formation. in these genes lead to the of cancer. One type of gene, a pro to- oncogene , is normally a transcription factor . When does not occur properly, detrimental effects can result.
    ::基因形成涉及两种主要的基因类型。 在这些基因中,有两种基因会导致癌症。 一种基因,一种是有利于致癌的基因,通常是一个转录系数。 如果基因形成不当,则可能产生有害影响。

    Regulation of Gene Expression in Cancer
    ::癌症基因表现条例

    Carcinogenesis is the process by which normal are transformed into cancer cells. The process is also known as oncogenesis or tumorigenesis and it depends on both the activation of oncogenes and deactivation of tumor suppressor genes . Proto-oncogenes , the non-cancerous normal version of an oncogene, can be a transcription factor like c-fos, c-jun and c-myc, or a gene whose product is involved in signal transduction , leading to altered . When mutations cause the regulation of this process to be disturbed, cell proliferation can be enhanced leading to tumorigenesis.
    ::肿瘤发源是正常转化为癌症细胞的过程,过程也称为肿瘤发源或肿瘤发源,这取决于肿瘤抑制基因的激活和肿瘤抑制基因的停止作用。 蛋白性蛋白,即非肿瘤正常的肿瘤发源,可以是一种转录系数,如c-fos、c-jun和c-myc,或一种产品涉及信号传输的基因,导致改变。 当突变导致该过程的调控受到干扰时,细胞扩散可导致肿瘤发源。

    At least two separate mutations are necessary to develop cancer. For example, a mutation in a proto-oncogene would not necessarily lead to cancer, as normally functioning tumor suppressor genes would counteract the effects of the oncogene. It is the second mutation in the tumor suppressor gene that could lead to uncontrolled cell growth and possibly cancer. Gene expression, signal transduction, the and oncogenes seem to have an interconnected relationship with each other inside the cell. Both oncogenes and tumor suppressor genes play an important role in gene regulation and cell proliferation ( Figure ). As stated above, numerous oncogenes are involved in gene expression. Signal transduction pathways are filled with involved in ultimately altering gene expression (see the : Signal Transduction (Advanced) concept). Anytime one of the involved proteins is altered, such as when its gene is mutated, gene expression can be altered.
    ::至少需要两种不同的突变才能发展癌症。例如,原生蛋白的突变不一定会导致癌症,因为正常运转的肿瘤抑制基因会抵消肿瘤的影响。肿瘤抑制基因的第二次突变可能导致细胞不受控制地生长并可能引发癌症。基因表达、信号转换、细胞内部的基因和肿瘤蛋白似乎相互联系。肿瘤抑制基因在基因调节和细胞扩散中起着重要作用(图示 )。如上所述,许多肿瘤抑制基因都与基因表达方式有关。信号传输途径被填满,最终改变基因表达方式(见:信号转换(高级)概念 ) 。 任何涉及的蛋白都可能发生改变,例如基因变异,基因表达方式可以改变。

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    How Cancer Develops. This flow chart shows how a series of mutations in tumor-suppressor genes and proto-oncogenes leads to cancer.
    ::癌症是如何发展的。这个流程图显示了肿瘤抑制基因和原生致癌基因的一系列突变是如何导致癌症的。

    Oncogenes
    ::肿瘤

    The products of proto-oncogenes are required for normal growth, repair and . However, when these genes are mutated, they turn into oncogenes and play a role in the development of cancer. Proto-oncogenes may be growth factors, , or other proteins involved in regulation. A very common oncogene, ras , is normally a regulatory GTPase that switches a signal transduction chain on and off. Ras and Ras-related proteins are products of oncogenes found in 20% to 30% of human tumors. The transcription factor myc is an oncogene often seen mutated in Burkitt’s lymphoma, a rare type of lymphoma, a cancer of the lymphocytes .
    ::蛋白质是正常生长、修复和修复所需的产物。 但是,当这些基因变异时,它们会变成肿瘤,并在癌症的发育中发挥作用。 蛋白质可能是生长因素,也可能是其他与调节相关的蛋白质。 一种非常常见的蛋白质(ras)通常是一种调节性GTPase,可以开关信号传输链的开关。 Ras和Ras相关的蛋白质是20-30 % 人类肿瘤中发现的肿瘤的产物。 抄录因子(Mic)是一种在Burkitt的淋巴瘤中常见的肿瘤,一种罕见的淋巴瘤,一种淋巴细胞癌。

    Ras is a G protein , a regulatory GTP hydrolase that cycles between an activated and inactivated form. When a growth factor binds to its receptor on the outside of the cell, a signal is relayed to Ras. As a G protein, Ras is activated when GTP is bound to it. The active Ras then passes the signal to a series of protein kinases, regulatory proteins that eventually activate transcription factors to alter gene expression and produce proteins that stimulate the cell cycle ( Figure ). One important recipient of Ras signaling is the mitogen-activated protein kinases (MAPK) . Once activated, MAPK transmit signals downstream to other protein kinases and gene regulatory proteins. This cascade of reactions is typical of a signal transaction pathway.
    ::Ras 是一种G蛋白质,一种调节性GTP 水解系统,在活性与非活性形式之间循环。当一个生长系数与细胞外部的受体结合时,一个信号被传送给Ras。作为G蛋白质,Ras在GTP受约束时被激活。活跃的Ras然后将信号传递给一系列蛋白类、调节性蛋白,最终激活转录系数以改变基因表达和产生刺激细胞循环的蛋白质(Figure ) 。Ras 信号的一个重要接收者是分子活性蛋白类(MAPK ) 。一旦激活,MAPK 将信号传送到下游其他蛋白类和基因调节性蛋白质。这一系列反应是信号交易路径的典型。

    Many of the genes and proteins involved in signal transduction pathways are interconnected to Ras. Any mutation that makes Ras more active or otherwise interrupts the normal signal transduction pathways ( Figure ) may result in excessive and cancer.
    ::信号传输路径所涉及的许多基因和蛋白质都与Ras连接。 任何让Ras更活跃或以其他方式中断正常信号传输路径的突变(图 ) 都可能导致过度和癌症。

    Tumor Suppressor Genes
    ::肿瘤抑制基因

    Tumor suppressor genes, as their name implies, normally suppress tumorigenesis. When this process is disturbed, such as by a mutation, tumor suppression may not be inhibited as normal. An example of a tumor suppressor gene is p53 , which encodes a 53,000 dalton (53kd) protein, The p53 gene is activated by damage. DNA may be damaged by ultraviolet light, and any damaged DNA may be harmful to the cell. Mutations causing problems with any of the components of Figure , may lead to the development of cancer. So that damaged DNA is not replicated, the cell cycle must be temporarily stopped so that the DNA can be repaired. The p53 tumor suppressor gene encodes a transcription factor that regulates the synthesis of cell cycle inhibiting proteins ( Figure ). p53 often activates a gene named p21, whose protein product temporarily stops the cell cycle. If the DNA can not be repaired, p53 activates other genes that lead to cell death, or apoptosis. This prevents the cell from passing on damaged DNA. If the p53 tumor suppressor gene is defective, as by mutation, DNA damage in the cell may accumulate and the cell may survive to replicate the damaged DNA. The damaged DNA would then be passed to other cells through many cell divisions, and cancer could develop.
    ::肿瘤抑制器基因的示例是p53, 肿瘤抑制器基因编码细胞循环合成抑制蛋白质(Figure)的转录因子。 p53 基因因损坏而激活。DNA可能受到紫外光的破坏,任何被损坏的DNA都可能对细胞有害。引起图中任何成分问题的突变可能导致癌症的发育。因此,如果不复制受损的DNA,就必须暂时停止细胞循环,以便修复DNA。如果P53肿瘤抑制器基因编码一个调制细胞循环合成抑制蛋白质(Figure )的转录因子。p53 基因通常会激活一个名为P21的基因,其蛋白质产品暂时停止细胞循环。如果DNA不能修复,第53页会激活其他导致细胞死亡的基因,或导致骨质紊乱。这样,细胞循环必须暂时停止,以便修复。如果P53肿瘤抑制器抑制器基因循环基因,则细胞基因基因基因基因会退化,通过基因基因变异,导致基因变异。

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    Signal transduction pathways. Ras (upper middle section) activates a number of pathways but an especially important one seems to be the mitogen-activated protein kinases (MAPK). MAPK transmit signals downstream to other protein kinases and gene regulatory proteins. Note that many of these pathways are initiated when a signal binds to its receptor outside the cell. Most pathways end with altered gene regulation and cell proliferation. The p53 tumor suppressor protein is shown at the lower section of the figure stimulating p21. The interrelated complexity of the pathways demonstrate the significant role these play in the cell.
    ::信号传输路径 。 Ras ( 上中段) 激活了许多路径, 但其中一种特别重要的路径似乎是 分子活性蛋白动脉( MAPK) 。 MAPK 将信号传送到下游其他蛋白动脉和基因调节蛋白质。 请注意, 许多这些路径是当信号与细胞外的受体连接时启动的。 大部分路径以改变基因调节和细胞扩散结束。 p53 肿瘤抑制蛋白在图的下一节显示刺激的 p21 。 路径的相互关联复杂性表明了这些路径在细胞中的重要作用 。

    Summary
    ::摘要

    • At least two separate mutations are necessary to develop cancer. These mutations may occur in proto-oncogenes and/or tumor suppressor genes.
      ::这些突变可能发生在原致癌和/或肿瘤抑制基因中。
    • Proto-oncogenes and tumor suppressor genes have an interconnected relationship within the cell; many are involved in signal transduction cascades.
      ::蛋白质蛋白质和肿瘤抑制基因在细胞内具有相互联系的关系;其中许多涉及信号感应级联。

    Review
    ::回顾

    1. What are proto-oncogenes and tumor suppressor genes?
      ::什么是原生蛋白质和肿瘤抑制基因?
    2. Discuss the two mutation models for tumorigenesis.
      ::讨论肿瘤起源的两个突变模型。
    3. How is signal transduction related to carcinogenesis?
      ::信号传输与致癌性的关系如何?
    4. Cancer is often the result of activation of ______ to ______ and the inactivation of ______ genes.
      ::癌症往往是至的激活和基因的丧失活化的结果。
    5. The p53 protein normally promotes ______.
      ::p53 蛋白质通常会促销 。
    6. The p53 gene is especially prone to _______.
      1. Point mutation.
        ::点突变
      2. Chromosomal rearrangement.
        ::染色体重新排列。
      3. Loss.
        ::损失。
      4. None of the above.
        ::上述情况无一例外。

      ::p53 基因特别容易发生... 点突变,染色体重新排列,损失,没有上述情况。
    7. A mutation in the ras gene can ______.
      1. Control cell division.
        ::控制细胞分部
      2. Inhibit cell division.
        ::隐居细胞分裂。
      3. Stimulate cell division.
        ::刺激细胞分裂
      4. Allow the ras gene to turn off.
        ::允许 ras 基因关闭 。

      ::拉斯基因的突变可以 . control cell division. inhibit cell division. 刺激细胞分裂。 允许 ras 基因关闭 。