Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1.
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.
Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
Wen-zhong
WZ
Wang
Hai-ou
HO
Liu
Yi-hong
YH
Wu
Yi
Y
Hong
Jun-wu
JW
Yang
Ye-heng
YH
Liu
Wei-bin
WB
Wu
Lei
L
Zhou
Lin-lin
LL
Sun
Jie-jie
JJ
Xu
Xiao-jing
XJ
Yun
Jian-xin
JX
Gu
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D051548:Histone Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone; D004958:Estradiol; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3