CA IX is upregulated in CoCl2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer
CA IX is upregulated in CoCl2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer
复制标题
DOI：
10.3892/ijo.2015.3253
复制
发表时间：
2016-01-01
影响因子：
5.2
通讯作者：
Zou, Qiang
中科院分区：
文献类型：
--
作者：
Chu, Cheng-Yu;Jin, Yi-Ting;Zou, Qiang
缺氧是包括乳腺癌在内的恶性实体瘤发展过程中的常见现象，其用于传播由缺氧诱导因子-1 α（HIF-1 α）触发的分子通路级联。碳酸酐酶IX（Carbonic anhydrase IX，CA IX）是HIF-1 α的靶基因之一，与恶性肿瘤的发生、发展密切相关。本研究的目的是探讨缺氧状态下HIF-1 α和CA IX的表达，CA IX在乳腺癌迁移和侵袭转移中的作用及其预后意义。我们使用氯化钴（CoCl 2）作为缺氧模拟剂，发现HIF-1 α蛋白，CA IX mRNA和蛋白的表达有效上调，除了HIF-1 α mRNA。研究表明，CA IX的高表达与体外细胞迁移和侵袭密切相关，其机制可能与上皮-间质转化（EMT）有关。临床组织样本的研究也表明CA IX是一个独立的预后标志物，可作为预测肿瘤进展和乳腺癌浸润/转移的有用的临床生物标志物。这些结果为进一步了解CA IX在肿瘤进展中的作用提供了新的见解，并为CA IX靶向治疗提供了进一步的有力证据和新的考虑。
Hypoxia, a common phenomenon during the development of malignant solid tumors including breast cancer, serves to propagate a cascade of molecular pathways triggered by hypoxia-inducible factor-1 alpha (HIF-1 alpha). Carbonic anhydrase IX (CA IX), one of the target genes of HIF-1 alpha, has been reported to be involved in progression of malignant tumors. The objective of this study was to investigate the expression of HIF-1 alpha and CA IX in hypoxia, involvement of CA IX in the regulation of migration and invasion/metastasis and its prognostic significance in breast cancer. We used cobalt chloride (CoCl2) as a hypoxia-mimetic agent and found that the expression of HIF-1 alpha protein, CA IX mRNA and protein, is effectively upregulated, except for HIF-1 alpha mRNA. Data showed that the elevated CA IX expression is closely related to in vitro cell migration and invasion, and the underlying mechanism of this process may be associated with epithelial-mesenchymal transition (EMT). The study of clinical tissue samples also demonstrated that CA IX is an independent prognostic marker that may serve as a useful clinical biomarker for predicting tumor progression and the invasion/metastasis of breast cancer. These results provide further insight into the role of CA IX in tumor progression and put forward further strong evidence as well as new consideration for CA IX target therapy.