Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway
Breast Cancer Invasion and Metastasis by mPRα Through the PI3K/Akt Signaling Pathway
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DOI：
10.1007/s12253-015-0023-8
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发表时间：
2016-07-01
影响因子：
2.8
通讯作者：
Ma, Rong
中科院分区：
文献类型：
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作者：
Wu, Xiaojuan;Sun, Limin;Ma, Rong
浸润性乳腺癌是世界范围内女性最常见的恶性肿瘤类型。然而，乳腺癌转移的机制仍不清楚，需要进一步阐明。已经证明基质金属肽酶9（MMP-9）促进癌细胞的转移。然而，尚未研究mPR α和MMP-9之间的相互作用。因此，在本研究中，研究了MMP-9对膜孕激素受体α（mPR α）促进的浸润性乳腺癌恶性进展的影响。结果显示，乳腺癌组织中mPR α、p-Akt和MMP-9蛋白表达均高于癌旁组织。此外，mPR α和C-erbB-2之间呈正相关，以及涉及的局部淋巴结的数量。另一方面，观察到mPR α与雌激素受体（ER）沿着孕激素受体（PR）之间呈负相关。同样，MMP-9与受累局部淋巴结数量呈正相关。MMP-9的高表达与肿瘤大小呈正相关。MMP-9与ER、PR呈负相关，mPR α、p-Akt与MMP-9呈正相关。结果证实mPR α是恶性肿瘤预后不良的主要标志物，它通过PI 3 K/Akt途径促进MMP-9在浸润局部淋巴结过程中的表达。本研究为通过阻断mPR α信号通路抑制乳腺癌生长提供了一种新的治疗策略。
Invasive breast cancer is the most common type of malignancy in women worldwide. However, the mechanism responsible for breast cancer metastasis is still unclear and needs further illustration. It has been proven that matrix metallopeptidase 9 (MMP-9) promotes metastasis of the cancer cells. However, the interaction between mPR alpha and MMP-9 has not been studied. Therefore, in the present research, the effect of MMP-9 on the malignant progression of invasive breast cancer promoted by membrane progesterone receptor alpha (mPR alpha) was investigated. The results showed that the protein expression of mPR alpha, p-Akt and MMP-9 increased in the cancerous tissues compared to that of the noncancerous breast tissue. Furthermore, a positive correlation was found between mPR alpha and C-erbB-2, as well as the number of involved local lymph nodes. On the other hand, a negative correlation was observed between mPR alpha and estrogen receptors (ER) along with progesterone receptors (PR). Similarly, a positive association was found between MMP-9 and the number of involved local lymph nodes. Besides, the high expression of MMP-9 also had a positive correlation with the tumor size. However, the high level of MMP-9 had a negative correlation with ER and PR. In addition, there was a positive correlation between mPR alpha and p-Akt together with MMP-9. The results confirm that mPR alpha was a major marker of harmful prognosis and it promoted the expression of MMP-9 during invasion to the local lymph nodes through the pathway of PI3K/Akt. The present study provided a novel therapeutic strategy to inhibit breast cancer growth by preventing mPR alpha signaling pathway.