Hbo1 Mechanism In Breast Cancer Research

The estrogen receptor alpha (ERalpha) is a member of the steriod receptor family, which is important for many biological processes and plays a key role in the pathogenesis of breast cancer. Estrogen receptor alpha (ERalpha), after binding its ligand, alters the transcription of target genes. This' genomic' signaling can be further divided into classical and nonclassical pathways. In Classica lsignaling, ERalpha binds to estrogen response elements (ERE) in target gene promoters and recruits cofactors to induce or repress transcription. In nonclassical signaling, ERalpha alters the transcription of genes without binding directly to an ERE. Rather ERalpha alters the activities of other transcription factors such as AP-1, Sp1, or NF-kB. Examples of genes known to be Hsp27, RANTES, IGF-1, VCAM-1, c-Myc, EGFR.HBO1 (human acetylase binding to ORC [1] is a MYST family histone acetylase that interacts both with transcriptional activator proteins [2] and with MCM2 [3],ORC1 [4], CDK11p58 [5], androgenreceptor (AR) [6], Cdt1 [7], ING4 and ING5 [8]. HBO1, an H4-specific histone acetylase, play a direct role at replication origins as a coactivator of the Cdt1 licensing factor and it is also involved in transcriptional regulation. HBO1 enhances transcription mediated by steroid receptors(ER and PR) and Interferes with Coactivator Functions [9], it is abundance in several cancer cell lines, over-expression of HBO1 (MYST2) dramatically enhanced the anchorage-independent growth of both MCF7 and SKBR3 breast cancer cells [10]. P53 Physically interacts with Hbo1 and negatively regulates its HAT activity invitro and in cells [11]. Those evidences suggest that this HAT maybe acandidate oncogene. In this study, we report that Hbo1 is overexpressed in breast cancer tissues and correlated with Tumour grade, Histology grade, ERalpha and PR expression by immunohistochemistry. Furthermore we found ERalpha drive the expression of hbo1 at transcriptional level. At last we found the effect of E2 on Hbo1 transcription is mediated through the Erk1/2 pathway.