Lian Y E, Wu D, Huang J P, Zheng Q L, Bai Y N, Feng C Y, Yang Y H
Department of Pathology, the Union Hospital of Fujian Medical University, Fuzhou 350001, China.
Department of Hepatobiliopancreatic Surgery, Fujian Provincial Hospital, Fuzhou 350001, China.
Zhonghua Bing Li Xue Za Zhi. 2020 Dec 8;49(12):1294-1299. doi: 10.3760/cma.j.cn112151-20200309-00186.
To investigate the expressions of HIF-1α, BRD4, Beclin1, LC3B and p62 in breast cancer tissues and their clinicopathological significance, and to study alterations of their expression in breast cancer cells under hypoxic microenvironment. Immunohistochemistry was used to detect HIF-1α, BRD4, Beclin1, LC3B and p62 protein expressions in 125 breast cancer tissues and 50 para-cancer normal breast tissues, and their correlation with clinicopathologic characteristics were analyzed. The expression of these proteins were also measured after 24 hours of hypoxia stimulation was detected in different breast cancer cell lines and normal breast epithelial cells. The expression of HIF-1α, BRD4, Beclin1 and LC3B proteins in breast cancer tissues were significantly higher than in para-cancer normal breast tissues (<0.05). There was a positive association between histologic grade, the expression of HIF-1α, BRD4, Beclin1 and LC3B (<0.05). High expressions of HIF-1a and Beclin1 were often correlated with lymph node metastasis and lymphatic invasion (<0.05). Increased HIF-1α, BRD4, Beclin1 and LC3B expression was associated with ER or PR negativity, but only HIF-1α was associated with HER2 positivity (<0.05). HIF-1α, BRD4, Beclin1, and LC3B were positively correlated with each other in breast cancer tissues (<0.01). After 24 hours of hypoxic stimulation, the expression of HIF-1α, BRD4, Beclin1 and LC3B was up-regulated in breast cancer cells. Hypoxia induces autophagy in breast cancer tissues. HIF-1α is positively correlated with BRD4, suggesting that BRD4 is involved in the regulation of autophagy by hypoxic microenvironment in breast cancer. High expression of HIF-1α, BRD4 and autophagy may play an important role in the development of breast cancer.
探讨HIF-1α、BRD4、Beclin1、LC3B和p62在乳腺癌组织中的表达及其临床病理意义，并研究其在低氧微环境下乳腺癌细胞中的表达变化。采用免疫组织化学法检测125例乳腺癌组织和50例癌旁正常乳腺组织中HIF-1α、BRD4、Beclin1、LC3B和p62蛋白的表达，并分析其与临床病理特征的相关性。在不同乳腺癌细胞系和正常乳腺上皮细胞中检测低氧刺激24小时后这些蛋白的表达。乳腺癌组织中HIF-1α、BRD4、Beclin1和LC3B蛋白的表达明显高于癌旁正常乳腺组织（<0.05）。组织学分级与HIF-1α、BRD4、Beclin1和LC3B的表达呈正相关（<0.05）。HIF-1α和Beclin1的高表达常与淋巴结转移和淋巴管浸润相关（<0.05）。HIF-1α、BRD4、Beclin1和LC3B表达增加与ER或PR阴性相关，但只有HIF-1α与HER2阳性相关（<0.05）。在乳腺癌组织中，HIF-1α、BRD4、Beclin1和LC3B彼此呈正相关（<0.01）。低氧刺激24小时后，乳腺癌细胞中HIF-1α、BRD4、Beclin1和LC3B的表达上调。低氧诱导乳腺癌组织中的自噬。HIF-1α与BRD4呈正相关，提示BRD4参与低氧微环境对乳腺癌自噬的调控。HIF-1α、BRD4的高表达及自噬可能在乳腺癌的发生发展中起重要作用。
