Clinicopathological relevance of UbcH10 in breast cancer
Clinicopathological relevance of UbcH10 in breast cancer
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DOI：
10.1111/j.1349-7006.2008.01026.x
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发表时间：
2009-02-01
期刊：
影响因子：
5.7
通讯作者：
Doihara, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Fujita, Takeo;Ikeda, Hirokuni;Doihara, Hiroyoshi
有丝分裂进程消失是癌症的常见标志。UbcH 10是泛素/蛋白酶体途径的一个组成部分，在有丝分裂进程的调节中起着关键作用。在某些类型的人类癌症中报告了异常的UbcH 10活性;与邻近的正常组织相比，在癌组织中偶尔会遇到其过度表达。目前的研究表明，UbcH 10在纺锤体组装检查点和随后的姐妹染色单体的准确分离中起着关键作用，这是由复杂多样的细胞周期机制所控制的一系列分子相互作用所协调的。为了验证UbcH 10在癌症细胞增殖中的潜在作用，我们使用人类肿瘤阵列和生化分析的组合方法分析了UbcH 10在乳腺癌进展中的临床病理学相关性。我们的研究结果表明，乳腺癌组织中UbcH 10染色阳性的测试样本的百分比显着高于相邻的非恶性组织。此外，从临床病理分析的结果表明，UbcH 10的表达升高与较高的组织学分级的肿瘤。此外，在乳腺癌细胞中通过RNA干扰耗尽UbcH 10导致细胞增殖降低，而UbcH 10的过表达显著增强乳腺癌细胞的生长。我们的研究结果表明UbcH 10和乳腺癌细胞增殖之间的病理相关性。因此，异常的UbcH 10活性可诱导正常细胞周期进程的功能障碍，并导致乳腺癌患者肿瘤细胞的侵袭行为。（Cancer Sci 2009; 100：238-248）。
Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer. (Cancer Sci 2009; 100: 238-248).