黑色素瘤缺乏蛋白2在癌症发展中的作用。
Absent in melanoma 2 proteins in the development of cancer.
作者信息
Choubey Divaker
机构信息
Research Service, Cincinnati VA Medical Center, 3200 Vine Street, ML-151, Cincinnati, OH, 45220, USA.
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, P. O. Box-670056, Cincinnati, OH, 45267, USA.
出版信息
Cell Mol Life Sci. 2016 Dec;73(23):4383-4395. doi: 10.1007/s00018-016-2296-9. Epub 2016 Jun 21.
Recent studies utilizing chemical-induced colitis-associated and sporadic colon cancer in mouse models indicated a protective role for absent in melanoma 2 (Aim2) in colon epithelial cells. Accordingly, mutations in the human AIM2 gene have been found in colorectal cancer (CRC), and reduced expression of AIM2 in CRC is associated with its progression. Furthermore, the overexpression of AIM2 protein in human cancer cell lines inhibits cell proliferation. Interferon-inducible Aim2 and AIM2 are members of the PYHIN (PYRIN and HIN domain-containing) protein family and share ~57 % amino acid identity. The family also includes murine p202, human PYRIN-only protein 3, and IFI16, which negatively regulate Aim2/AIM2 functions. Because the CRC incidence and mortality rates are higher among men compared with women and the expression of Aim2/AIM2 proteins and their regulators is dependent upon age, gender, and sex hormones, we discuss the potential roles of Aim2/AIM2 in the development of cancer. An improved understanding of the biological functions of the AIM2 in the development of CRC will likely identify new therapeutic approaches to treat patients.
最近利用化学诱导的结肠炎相关和散发性结肠癌小鼠模型进行的研究表明，黑色素瘤2（Aim2）在结肠上皮细胞中具有保护作用。因此，在结直肠癌（CRC）中发现了人类AIM2基因的突变，并且CRC中AIM2表达的降低与其进展相关。此外，人类癌细胞系中AIM2蛋白的过表达抑制细胞增殖。干扰素诱导的Aim2和AIM2是含PYHIN（含PYRIN和HIN结构域）蛋白家族的成员，氨基酸同一性约为57%。该家族还包括小鼠p202、人类仅含PYRIN蛋白3和IFI16，它们对Aim2/AIM2功能起负调节作用。由于男性的CRC发病率和死亡率高于女性，且Aim2/AIM2蛋白及其调节因子的表达取决于年龄、性别和性激素，我们讨论了Aim2/AIM2在癌症发生中的潜在作用。对AIM2在CRC发生中的生物学功能有更深入的了解可能会确定治疗患者的新方法。
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