Estrogen receptor (ER) mediates 17-estradiol (E2)-activated expression of HBO1

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 (ER) (p < 0.001) and progestational hormone (PR) (p = 0.002). HBO1 protein level also correlated positively with histology grade in ER positive tumors (p = 0.016) rather than ER negative tumors. 17-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ER 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 ER, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2. © 2010 Wang et al; licensee BioMed Central Ltd.