Polycomb Group genes in murine lymphomagenesisand their impact on drug response.

小鼠淋巴瘤发生中的多梳族基因及其对药物反应的影响。

• 批准号: nhmrc : 461261
• 负责人: A/Pr Clare Scott
• 金额: $ 31.79万
• 依托单位: The Walter and Eliza Hall Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/polycomb-group-genes-drug-response/81110
• 关键词: Polycomb; Group; genes; murine; lymphomagenesisand

The success of lymphoma treatment with current drugs is limited by drug resistance. Some crucial links between genes which cause cancer and genes which alter response to cancer treatment have been identified: the cellular machinery that cancer cells use to become cancer cells in the first place, is often the same machinery that cancer cells later use to become resistant to cancer treatments. The Polycomb Group family controls expression of other critical genes: that is, they dictate which genes are switched on, where, and when. This determines whether a cell behaves normally or whether it may turn into a cancer cell. When Polycomb Group genes themselves are expressed at the wrong time or place, they can cause cancer. In human lymphoma, these genes have been associated with more aggressive lymphoma. This has also been shown for other cancers such as breast and prostate cancer. In some cases these genes are associated with cancers that do worse following anti-cancer treatment. So far, no research has been published looking the direct impact of the Polycomb Group genes on the success of treatment in a controlled laboratory model. We have used a powerful laboratory mouse model of lymphoma, established in the host laboratory, in which over-expression of the c-myc oncogene in developing B cells causes lymphoma. This model is easy to manipulate and this provides us with a great deal of experimental control, much more than can be achieved from working with patient samples. Two family members, Bmi-1 and Cbx7, cause lymphoma to develop aggressively and we will ask whether two other members, Ezh2 and Rybp do this as well. We will determine whether these 4 genes cause drug resistance in lymphoma, with currently used chemotherapy and also with novel anti-cancer drugs. By increasing our understanding of drug resistance in lymphoma, drugs may be utilised more effectively and new markers identified to predict which drug will be successful in treating a particular lymphoma.

用当前药物治疗淋巴瘤的成功受到耐药性的限制。导致癌症的基因和改变对癌症治疗反应的基因之间的一些关键联系已经被确定：癌细胞最初用来成为癌细胞的细胞机制，通常与癌细胞后来用来抵抗癌症治疗的机制相同。Polycomb Group家族控制着其他关键基因的表达：也就是说，它们决定了哪些基因在何时何地被打开。这决定了一个细胞是否表现正常，或者它是否可能变成癌细胞。当Polycomb Group基因本身在错误的时间或地点表达时，它们可能会导致癌症。在人类淋巴瘤中，这些基因与更具侵袭性的淋巴瘤相关。其他癌症如乳腺癌和前列腺癌也显示了这一点。在某些情况下，这些基因与抗癌治疗后恶化的癌症有关。到目前为止，还没有研究发表在受控实验室模型中寻找Polycomb Group基因对治疗成功的直接影响。我们已经使用了一个强大的实验室小鼠淋巴瘤模型，建立在宿主实验室，其中过度表达的c-myc癌基因在发展中的B细胞导致淋巴瘤。这个模型很容易操作，这为我们提供了大量的实验控制，远远超过可以从病人样本的工作。两个家庭成员，Bmi-1和Cbx 7，导致淋巴瘤发展积极，我们将问是否其他两个成员，Ezh 2和Rybp这样做，以及。我们将确定这4个基因是否会导致淋巴瘤的耐药性，与目前使用的化疗和新型抗癌药物。通过增加我们对淋巴瘤耐药性的了解，可以更有效地利用药物，并确定新的标记物来预测哪种药物将成功治疗特定的淋巴瘤。