1. Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1.
- Author
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Wang WZ, Liu HO, Wu YH, Hong Y, Yang JW, Liu YH, Wu WB, Zhou L, Sun LL, Xu JJ, Yun XJ, and Gu JX
- Subjects
- Blotting, Western, Breast Neoplasms genetics, Cell Line, Tumor, Estradiol genetics, Estrogen Receptor alpha genetics, Female, Gene Expression, Histone Acetyltransferases genetics, Humans, Immunohistochemistry, Mitogen-Activated Protein Kinase 1 genetics, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 genetics, Mitogen-Activated Protein Kinase 3 metabolism, Receptors, Progesterone genetics, Receptors, Progesterone metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Transfection, Breast Neoplasms metabolism, Estradiol metabolism, Estrogen Receptor alpha metabolism, Gene Expression Regulation, Neoplastic, Histone Acetyltransferases biosynthesis
- Abstract
Background: HBO1 (histone acetyltransferase binding to ORC1) is a histone acetyltransferase (HAT) which could exert oncogenic function in breast cancer. However, the biological role and underlying mechanism of HBO1 in breast cancer remains largely unknown. In the current study, we aimed to investigate the role of HBO1 in breast cancer and uncover the underlying molecular mechanism., Methods: Immunohistochemistry was applied to detect HBO1 protein expression in breast cancer specimens (n=112). The expression of protein level was scored by integral optical density (IOD) for further statistical analyses using SPSS. Real-time PCR was used to simultaneously measure mRNA levels of HBO1. The HBO1 protein expression in breast cancer cells was confirmed by western blot., Results: HBO1 was highly expressed in breast cancer tissues and significantly correlated with estrogen receptor α (ERα) (p<0.001) and progestational hormone (PR) (p=0.002). HBO1 protein level also correlated positively with histology grade in ERα positive tumors (p=0.016) rather than ERα negative tumors. 17β-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ERα RNAi. E2-increased HBO1 protein expression was significantly suppressed by treatment with inhibitor of MEK1/2 (U0126) in T47 D and MCF-7 cells., Conclusions: HBO1 was an important downstream molecule of ERα, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2.
- Published
- 2010
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