Expression of MAS1 in breast cancer.
Expression of MAS1 in breast cancer.
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DOI：
10.1111/cas.12719
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发表时间：
2015-09
期刊：
影响因子：
5.7
通讯作者：
Kuniyasu H
中科院分区：
文献类型：
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作者：
Luo Y;Tanabe E;Kitayoshi M;Nishiguchi Y;Fujiwara R;Matsushima S;Sasaki T;Sasahira T;Chihara Y;Nakae D;Fujii K;Ohmori H;Kuniyasu H
MAS 1是血管紧张素1-7（A1-7）的受体，其通过血管紧张素转化酶（ACE）2的作用衍生自血管紧张素II（A-II）。MAS 1诱导抗A-II表型，如血管扩张和血压降低。利用免疫组化方法，我们研究了MAS 1在132例乳腺浸润性导管癌（IDC）中的作用。而良性乳腺组织表达MAS 1在高水平，MAS 1的表达减弱，在所有IDC，特别是在硬癌IDC。MAS 1表达的降低与肿瘤生长、淋巴结转移和分级相关。MAS 1表达与增殖指数、表皮生长因子受体和人表皮生长因子受体-2表达呈负相关。132例中，12例（9.1%）为三阴性乳腺癌（TNBC）病例。所有TNBC病例（12例病例和使用组织阵列的另外36例病例）均表达MAS 1。使用表达MAS 1的TNBC细胞系4 T1和MDA-MB-468，我们发现细胞生长、抗凋亡存活和侵袭被用A1-7处理的MAS 1活化抑制，并被MAS 1敲低增强。与此相反，三苯氧胺和A1-7之间的协同作用被发现在管腔A乳腺癌细胞系，MCF-7。在同系小鼠模型中，顺铂、ACE 2激活剂和A-II 1型受体阻断剂的联合治疗对4 T1肿瘤的肿瘤生长抑制具有协同作用。这些发现表明，MAS 1可能作为乳腺癌的抑制性调节剂，并可能是这种恶性肿瘤的一个可能的分子靶点。
MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. MAS1 induces anti-A-II phenotypes, such as vessel dilation and depression of blood pressure. Using immunohistochemistry, we examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast. While benign mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDC, especially in scirrhous IDC. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. All TNBC cases (the 12 cases and the additional 36 cases using a tissue array) expressed MAS1. Using the TNBC cell lines 4T1 and MDA-MB-468, which expresses MAS1, we found that cell growth, anti-apoptotic survival and invasion were suppressed by MAS1 activation with A1-7 treatment and enhanced by MAS1 knockdown. In contrast, synergic effect was found between tamoxifen and A1-7 in a luminal A breast cancer cell line, MCF-7. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition of 4T1 tumors in a syngeneic mouse model. These findings suggest that MAS1 might act as an inhibitory regulator of breast cancer and may be a possible molecular target for this malignancy.