文章目录

黑腹果蝇：一种研究恶性肿瘤和确定新疗法的模型和工具

Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics

原文发布日期：2013-02-07

DOI: 10.1038/nrc3461

类型: Review Article

开放获取: 否

要点：

要点翻译：

英文摘要：

摘要翻译：

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文章：

黑腹果蝇：一种研究恶性肿瘤和确定新疗法的模型和工具

Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics

原文发布日期：2013-02-07

DOI: 10.1038/nrc3461

类型: Review Article

开放获取: 否

要点：

For a century, seemingly non-applied research carried out in Drosophila melanogaster has provided the first glimpse into the mechanism of action of human cancer-related proteins.
Natural malignant tumours can occur in D. melanogaster.
Tumours can also be experimentally induced in larvae and adult flies either by knocking down fly tumour suppressor genes or by recreating in flies the mutant conditions that are causative of certain human cancer types. Current examples of this 'a la carte' design include cancer models of glioblastoma, rhabdomyosarcoma, multiple endocrine neoplasia and leukaemia.
D. melanogaster tumours range from hyperplasias to frankly malignant neoplasias that are invasive and lethal to the host.
Both the presence and the lack of supernumerary centrosomes can cause tumours in the larval brain, but unbalanced karyotypes do not. Thus, in D. melanogaster, Boveri's hypothesis does not apply, but centrosome dysfunction is linked to cancer.
The origin of the widespread genome instability that is characteristic of cancer cells is likely to be multifactorial.
The loss of cell polarity in cells that divide asymmetrically, as well as in epithelial tissues, is often tumorigenic.
The Aurora and POLO protein kinases are tumour suppressors in the larval brain.
The activation of signalling pathways that sense low calorie intake and inhibit target of rapamycin (TOR) compromises cortical polarity and contributes to tumour growth.
Data derived from D. melanogaster strongly substantiate the view that timely repression of gene expression programmes during development has a pronounced tumour suppression function.
D. melanogaster lethal (3) malignant brain tumour (l(3)mbt) tumours recapitulate the ectopic expression of cancer germline (CG; also known as cancer testis (CT)) genes that are observed in many types of somatic human tumours. In D. melanogaster, inactivation of some CG genes inhibits tumour growth.
D. melanogaster is starting to have an important role in chemical genetics, helping to identify the pathways that are affected by current pharmaceuticals, facilitating the design of more efficient derivatives and serving as a platform for semi-automated screens for new anticancer drugs.

要点翻译：

一个世纪以来，在黑腹果蝇身上进行的看似非应用性研究首次揭示了人类癌症相关蛋白的作用机制。
黑腹果蝇体内可自然发生恶性肿瘤。
通过敲除果蝇抑癌基因或重现导致某些人类癌症类型的突变条件，也能在幼虫和成年果蝇中实验性诱导肿瘤。当前这种"按需定制"模型的实例包括胶质母细胞瘤、横纹肌肉瘤、多发性内分泌腺瘤病和白血病等癌症模型。
黑腹果蝇的肿瘤范围从增生性病变到具有侵袭性且致宿主死亡的明显恶性赘生物。
额外中心体的存在与缺失均可导致幼虫脑部肿瘤，但核型不平衡则不会。因此，鲍维里假说在黑腹果蝇中并不适用，但中心体功能障碍与癌症存在关联。
癌细胞普遍存在的基因组不稳定性特征很可能由多因素共同导致。
在不对称分裂的细胞及上皮组织中，细胞极性的丧失通常具有致瘤性。
极光激酶和POLO蛋白激酶在幼虫大脑中发挥抑癌作用。
感知低热量摄入并抑制雷帕霉素靶蛋白（TOR）的信号通路激活会损害皮质极性，进而促进肿瘤生长。
来自黑腹果蝇的数据充分证实：在发育过程中适时抑制基因表达程序具有显著的肿瘤抑制功能。
黑腹果蝇致死(3)恶性脑肿瘤（l(3)mbt）模型重现了在多种人类体细胞肿瘤中观察到的癌性生殖系（CG，亦称癌睾丸CT）基因异位表达现象。在黑腹果蝇中，某些CG基因的失活可抑制肿瘤生长。
黑腹果蝇正开始在化学遗传学领域发挥重要作用：协助识别现有药物影响的信号通路，促进更高效衍生物的设计，并作为新型抗癌药物半自动化筛选平台。

英文摘要：

For decades, lower-model organisms such as Drosophila melanogaster have often provided the first glimpse into the mechanism of action of human cancer-related proteins, thus making a substantial contribution to elucidating the molecular basis of the disease. More recently, D. melanogaster strains that are engineered to recapitulate key aspects of specific types of human cancer have been paving the way for the future role of this 'workhorse' of biomedical research, helping to further investigate the process of malignancy, and serving as platforms for therapeutic drug discovery.

摘要翻译：

数十年来，低等模式生物如果蝇（Drosophila melanogaster）常常为人类癌症相关蛋白作用机制提供初步线索，为阐明疾病的分子基础作出重要贡献。近年来，经过基因工程改造、能重现特定人类癌症关键特征的果蝇品系，正为这一“生物医学研究主力”的未来角色铺平道路，助力深入研究恶性转化过程，并作为治疗性药物发现的平台。