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Breast cancer has become the most common malignant tumor in the world. Heat shock protein 90 (HSP90) is a kind of molecular chaperone which can promote protein folding and maintain protein stability. HSP90 includes HSP90α, HSP90β, GRP94 and TRAP1 subtypes. Previous studies have found that the level of HSP90 is significantly increased in malignant tumors such as breast cancer, and is closely related to the occurrence and development of tumors. Meanwhile, the research on inhibitors targeting HSP90 has also attracted much attention. In this paper, we reviewed the expression of four HSP90 subtypes in breast cancer and their relationship with the clinicopathologic feature and prognosis of patients, discussed the research progress of specific inhibitors of HSP90 subtypes in breast cancer, and analyzed the application prospect of HSP90 as biomarkers for breast cancer prognosis monitoring and therapeutic targets.
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Objective:To investigate the relationship between single nucleotide polymorphism (SNPs) of Zeste homolog enhancer 2 (EZH2) gene and the risk of breast cancer.Methods:Recruiting 1 039 breast cancer patients and 1 040 controls at 22 referral hospitals nationwide in China, the genotype distribution of 3 SNPs loci of EZH2 genes was observed to detect the correlation between different genotypes and the risk of breast cancer genotypes EZH2 expression in breast cancer tissues and its correlation with patient prognosis were analyzed using breast cancer data from the database.Results:EZH2 rs6464926 CC genotype was compared with TT genotype (TT vs. CC: OR=1.362, 95% CI: 1.063-1.746, P=0.015) and dominant model (TC+TT vs .CC: OR=1.22, 95% CI: 1.004-1.483, P=0.045) .In women with BMI ≥24 kg/m 2, the TC genotype ( P=0.050), TT genotype ( P=0.025) and dominant model (TC+TT, P=0.021) of rs6464926 locus were significantly different from CC genotype in cancer risk. rs6464926 was correlated with EZH2 gene expression ( P=6.89E-47). EZH2 gene is highly expressed in breast cancer tissues, and patients with high expression were associated with shorter OS ( HR=1.27, P=0.013), DMFS ( HR=1.37, P<0.01), and RFS ( HR=1.44, P<0.01). Conclusions:The polymorphism rs6464926 of EZH2 gene is associated with breast cancer susceptibility in Chinese women. rs6464926 might regulate breast cancer risk and prognosis by changing EZH2 expression.
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OBJECTIVE@#To investigate the effect of medium-chain acyl-CoA dehydrogenase (ACADM) on invasion and metastasis of breast cancer cells and explore the underlying mechanism.@*METHODS@#A large cancer genome database was used to analyze the expression of ACADM in breast cancer tissues and normal tissues. The proliferation, migration and invasion of cultured breast cancer MCF-7 and T47D cells with ACADM overexpression or ACADM silencing were evaluated using MTT proliferation assay, EdU assay, Transwell chamber assay, and Boyden invasion assay; Western blotting was used to detect the protein expressions of the related pathway in the cells. In nude mouse models of tail vein metastasis of MCF-7 cells with or without ACADM overexpression, the tumor growth and tumor histopathology were observed using HE staining.@*RESULTS@#Analysis of the Oncomine sample set showed a significantly higher expression level of ACADM in breast cancer tissues than in normal breast tissues ( < 0.05). Overexpression of ACADM obviously enhanced the migration and invasion abilities and promoted the epithelial-mesenchymal transition (EMT) of cultured MCF-7 and T47D cells; conversely, silencing of ACADM significantly suppressed the migration and invasion of the breast cancer cells. In the nude mouse models, ACADM overexpression in MCF-7 cells significantly enhanced their migration and invasion abilities.@*CONCLUSIONS@#ACADM can promote the EMT process of breast cancer cells and improve the migration and invasion ability. ACADM is an oncogene in breast cancer.