[Effect of HIF-1α and BRD4 on autophagy level of breast cancer cell in hypoxic microenvironment].

ABSTRACT

Objective: 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. Methods: 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. Results: The expression of HIF-1α, BRD4, Beclin1 and LC3B proteins in breast cancer tissues were significantly higher than in para-cancer normal breast tissues (P<0.05). There was a positive association between histologic grade, the expression of HIF-1α, BRD4, Beclin1 and LC3B (P<0.05). High expressions of HIF-1a and Beclin1 were often correlated with lymph node metastasis and lymphatic invasion (P<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 (P<0.05). HIF-1α, BRD4, Beclin1, and LC3B were positively correlated with each other in breast cancer tissues (P<0.01). After 24 hours of hypoxic stimulation, the expression of HIF-1α, BRD4, Beclin1 and LC3B was up-regulated in breast cancer cells. Conclusions: 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.