The impact of CBP expression in estrogen receptor-positive breast cancer

Abstract

Background: The development of new biomarkers with diagnostic, prognostic and therapeutic prominence will greatly enhance the management of breast cancer (BC). Several reports suggest the involvement of the histone acetyltransferases CREB-binding protein (CBP) and general control non-depressible 5 (GCN5) in tumor formation; however, their clinical signifcance in BC remains poorly understood. This study aims to investigate the value of CBP and GCN5 as markers and/or targets for BC prognosis and therapy. Expression of CBP, GCN5, estrogen receptor α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in BC was analyzed in cell lines by western blot and in patients’ tissues by immunohistochemistry. The gene amplifcation data were also analyzed for CBP and GCN5 using the publicly available data from BC patients.

Results: Elevated expression of CBP and GCN5 was detected in BC tissues from patients and cell lines more than normal ones. In particular, CBP was more expressed in luminal A and B subtypes. Using chemical and biological inhibi tors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreo ver, analysis of the CREBBP (for CBP) and KAT2A (for GCN5) genes in a larger number of patients in publicly available databases showed amplifcation of both genes in BC patients. Amplifcation of CREBBP gene was observed in luminal A, luminal B and triple-negative but not in HER2 overexpressing subtypes. Furthermore, patients with high CREBBP or KAT2A gene expression had better 5-year disease-free survival than the low gene expression group (p=0.0018 and p<0.00001 espectively).

Conclusions: We conclude that the persistent amplifcation and overexpression of CBP in ERα- and PR-positive BC highlights the signifcance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.