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Neoplasma Vol.62, No.3, p.456-463, 2015 |
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Title: Correlation between carbonic anhydrase IX (CA-9), XII (CA-12) and hypoxia inducible factor-2α (HIF-2α) in breast cancer | ||
Author: J. JIANG, J. H. ZHAO, X. L. WANG, X. J. GUO, J. YANG, X. BAI, S. Y. JIN, R. L. GE | ||
Abstract: Hypoxia inducible factor 2α (HIF-2α) can trigger the expression of several genes related to many aspects of tumor progress under hypoxia. As an independent factor, the role of HIF-2α is different from other hypoxia-mediated elements, including HIF-1α. Carbonic anhydrase (CA) were also regarded as important enzymes that involve in the tumor microenvironment pH. To find clinical-pathological features of breast cancer in plateau and explore the impact of CAIX, XII (CA-9, CA-12) and HIF-2α on patients with breast cancer. Clinical data were collected and summarized in 94 patients with breast cancer. The expression of HIF-2α, CA-9 and CA-12 were detected, using immunohistochemistry of specimens. The relation between expressions and clinical-pathology was analyzed. Under normoxia, hypoxia, and after being pretreated with the JNK inhibitor SP600125, HIF- 2α, CA-9 and CA-12 expressions were detected, and adhesion and invasion assays were performed in MCF-7 cells and HIF- 2α shRNA cells, respectively. There are higher expressions of HIF-2α in tumor classification 2 and clinical stage 2 (P < 0.05). High expression of CA-12 was observed in clinical stage 2 (P < 0.05). CA-9 expression is significantly correlated with CA-12 expression (r = 0.376, P = 0.0001). HIF-2α expression is not correlated with both CA-9 expression (P = 0.21) and CA-12 expression (P = 0.27). Breast cancer cells in vitro showed that HIF-2α, CA-9 or CA-12 had an increase expression under hypoxia (1% O2). CA-9 or CA-12 expression was observed in HIF-2α shRNA cells. JNK inhibitor SP 600125 reduced the HIF-2α expression and inhibited the adhesion and invasion of breast cancer cell. Slight inhibition effect on CA-9 and CA-12 expression was found. In conclusion, HIF-2α, CA-9 and CA-12 are important hypoxia responsive elements in breast cancer. HIF-2α was involved in metastasis and invasion of breast cancer cells under hypoxia, by the involvement of c-Jun NH2-terminal kinase (JNK) signal pathway. CA-9 and CA-12 may tend to be regulated by HIF-1α more often than by HIF-2α under hypoxia. |
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Keywords: breast cancer, carbonic anhydrase, hypoxia | ||
Published online: 01-Apr-2015 | ||
Year: 2015, Volume: 62, Issue: 3 | Page From: 456, Page To: 463 | |
doi:10.4149/neo_2015_054 |
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