Wang et al. Journal of Experimental & Clinical Cancer Research 2010, 29:140 http://www.jeccr.com/content/29/1/140 R E S E A R C H Open Access Estrogen receptor a (ERa) mediates 17b-estradiol (E2)-activated expression of HBO1 Wen-zhong Wang1†, Hai-ou Liu1,3†, Yi-hong Wu1, Yi Hong1, Jun-wu Yang1, Ye-heng Liu2, Wei-bin Wu2, Lei Zhou1, Lin-lin Sun1,3, Jie-jie Xu1*, Xiao-jing Yun1*, Jian-xin Gu2 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 a (ERa) (p < 0.001) and progestational hormone (PR) (p = 0.002). HBO1 protein level also correlated positively with histology grade in ERa positive tumors (p = 0.016) rather than ERa negative tumors. 17b-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ERa 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 ERa, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2. Background Breast cancer is a major public health issue, with more than one million new cases observed around the world in 2002 [1]. The pathogenesis of breast cancer is quite com- plex. Lifetime exposure to estrogen is reported to be asso- ciated with women’s risk for breast cancer and the biological actions of estrogens are mediated primarily by ERa which belongs to the nuclear receptor superfamily, a family of ligand-regulated transcription factors [2-4]. ERa, which promotes cell growth, metastasis and also mediates resistance to apoptosis, plays a key role in progression of breast cancer [5,6]. HBO1 (histone acetyltransferase binding to ORC1), also named MYST2, belongs to the MYST family which is * Correspondence: jjxufdu@hotmail.com; xjyun@fudan.edu.cn † Contributed equally 1Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, 200032, China Full list of author information is available at the end of the article characterized by a highly conserved C2HC zinc finger and a putative histone acetyltransferase domain. The role of HBO1 in cancer remains unclear, although its expression has been reported in testicular germ cell tumors, breast adenocarcinomas, and ovarian serous carcinomas [7]. Recent investigations have revealed that over-expression of HBO1 dramatically enhances the anchorage-indepen- dent growth of both MCF7 and SKBR3 breast cancer cells [8]. Furthermore, it also functions as a transcriptional coactivator for hormone receptors including ERa and PR [9], leading to consideration of this protein as a carcinoge- netic factor. To elucidate the role of HBO1 in breast cancer, 112 breast cancer specimens were investigated using immu- nohistochemistry with an anti-HBO1 antibody. We found that HBO1 was notably increased in breast cancer. E2-upregulated HBO1 expression could be inhibited by ICI 182,780 or ERa RNAi in breast cancer cells. © 2010 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.