TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.
TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.
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DOI：
10.1002/cam4.736
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发表时间：
2016-08
期刊：
影响因子：
4
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Onodera Y;Takagi K;Miki Y;Takayama K;Shibahara Y;Watanabe M;Ishida T;Inoue S;Sasano H;Suzuki T
转化型酸性卷曲蛋白2(TACC2)属于TACC家族蛋白，通过与中心体/微管动力学相关分子的相互作用参与多种细胞过程。越来越多的证据表明，TACCs与某些人类恶性肿瘤的发生发展有关，但TACC2蛋白在乳腺癌中的意义尚不清楚。因此，在本研究中，我们通过免疫组织化学和体外实验研究了TACC2在乳腺癌中的临床意义和生物学功能。应用免疫组织化学方法检测154例浸润性导管癌组织中TACC2的表达。将针对TACC2的小干扰RNA(SiRNA)导入乳腺癌细胞株MCF-7和MDA-MB-453，进行细胞增殖、5-溴-2‘-脱氧尿苷(BrdU)检测和侵袭实验。在154例乳腺癌组织中，78例(51%)表达TACC2，且TACC2与Ki-67LI显著相关。免疫组织化学TACC2状态与患者复发和乳腺癌特异性死亡的增加显著相关，多因素分析表明TACC2状态是无病生存和乳腺癌特异性生存的独立预后因素。随后的体外实验表明，TACC2能显著增强MCF-7和MDA-MB-453细胞的增殖活性。这些结果表明，TACC2在乳腺癌的细胞增殖中起重要作用，因此免疫组织化学TACC2状态是乳腺癌患者预后较差的候选因素。
Transforming acidic coiled‐coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF‐7 and MDA‐MB‐453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5‐Bromo‐2′‐deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki‐67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer‐specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease‐free and breast cancer‐specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF‐7 and MDA‐MB‐453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases.