Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1

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.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.HBO1 was an important downstream molecule of ERα, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2.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 complex. Lifetime exposure to estrogen is reported to be associated with women's risk for breast cancer and the biological actions of estrogens are mediated primarily by ERα which belongs to the nuclear receptor superfamily, a family of ligand-regulated transcription factors [2-4]. ERα, 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 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 adenocar