Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma.
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DOI:
10.1267/ahc.16020
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发表时间:
2016-11-01
影响因子:
2.4
通讯作者:
Nemoto N
Nemoto N
中科院分区:
生物学4区
文献类型:
--
作者:
Murakami E;Nakanishi Y;Hirotani Y;Ohni S;Tang X;Masuda S;Enomoto K;Sakurai K;Amano S;Yamada T;Nemoto N

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乳腺癌由于肿瘤细胞侵袭和转移,预后较差。虽然Ras同源物(Rho) A参与肿瘤细胞侵袭,但其在乳腺癌中的作用尚不清楚。本研究检测了RhoA在浸润性导管癌(IDC)中的表达,重点研究了其与表皮-间充质转化(EMT)和集体细胞侵袭的关系。获得44例手术IDC组织样本和2例正常乳腺组织样本。免疫组织化学分析RhoA、E-cadherin、vimentin和F-actin蛋白的表达。RhoA、ROCK、mTOR、AKT1和PIK3CA mRNA的表达采用激光显微解剖和半巢式定量逆转录聚合酶链反应。RhoA在肿瘤界面的表达强于肿瘤中心(P<0.001)。RhoA表达仅在her2亚型IDC中与ROCK表达相关(P<0.05)。在共表达RhoA和ROCK的idc中,F-actin在肿瘤界面上的表达强于ROCK阴性idc (P<0.0001),尤其是在肿瘤细胞边缘。综上所述,IDC中RhoA的表达与EMT无关,而F-actin的表达增强则定位于共表达ROCK的肿瘤细胞边缘。RhoA/ROCK信号可能与集体细胞侵袭有关,特别是在her2亚型IDC中。
Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.
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