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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7(+/-) mouse
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Haploinsufficiency of Anx7 tumor suppressor gene and consequent genomic instability promotes tumorigenesis in the Anx7(+/-) mouse

机译：Anx7肿瘤抑制基因的单倍不足和随之而来的基因组不稳定性促进Anx7（+/-）小鼠的肿瘤发生。

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Annexin 7 (ANX7) acts as a tumor suppressor gene in prostate cancer, where loss of heterozygosity and reduction of ANX7 protein expression is associated with aggressive metastatic tumors. To investigate the mechanism by which this gene controls tumor development, we have developed an Anx7(+/-) knockout mouse. As hypothesized, the Anx7(+/-) mouse has a cancer-prone phenotype. The emerging tumors express low levels of Anx7 protein. Nonetheless, the wild-type Anx7 allele is detectable in laser-capture microdissection-derived tumor tissue cells. Genome array analysis of hepatocellular carcinoma tissue indicates that the Anx7(+/-) genotype is accompanied by profound reductions of expression of several other tumor suppressor genes, DNA repair genes, and apoptosis-related genes. In situ analysis by tissue imprinting from chromosomes in the primary tumor and spectral karyotyping analysis of derived cell lines identify chromosomal instability and clonal chromosomal aberrations. Furthermore, whereas 23% of the mutant mice develop spontaneous neoplasms, all mice exhibit growth anomalies, including gender-specific gi-gantism and organomegaly. We conclude that haploinsufficiency of Anx7 expression appears to drive disease progression to cancer because of genomic instability through a discrete signaling pathway involving other tumor suppressor genes, DNA-repair genes, and apoptosis-related genes.
机译：Annexin 7（ANX7）在前列腺癌中起着抑癌基因的作用，其中杂合性的丧失和ANX7蛋白表达的降低与侵袭性转移性肿瘤有关。为了研究该基因控制肿瘤发展的机制，我们开发了Anx7（+/-）基因敲除小鼠。如所假设的，Anx7（+/-）小鼠具有易癌的表型。新兴的肿瘤表达低水平的Anx7蛋白。但是，野生型Anx7等位基因可在激光捕获显微切割衍生的肿瘤组织细胞中检测到。肝细胞癌组织的基因组阵列分析表明，Anx7（+/-）基因型伴随着其他几种抑癌基因，DNA修复基因和凋亡相关基因的表达大大降低。通过从原发性肿瘤中的染色体上组织印记进行原位分析，并对衍生的细胞系进行光谱核型分析，可确定染色体的不稳定性和克隆的染色体畸变。此外，尽管有23％的突变小鼠出现自发性肿瘤，但所有小鼠均表现出生长异常，包括性别特异性巨人症和器官肿大。我们得出结论，由于基因组不稳定性通过涉及其他肿瘤抑制基因，DNA修复基因和凋亡相关基因的离散信号通路而引起的基因组不稳定性，Anx7表达的单倍不足似乎导致疾病发展为癌症。

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