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 significance 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 amplification 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 inhibitors for CBP, ERα and HER2 showed a strong association between CBP and the expression of ERα and HER2. Moreover, analysis of the CREBBP (for CBP) and KAT2A (for GCN5) genes in a larger number of patients in publicly available databases showed amplification of both genes in BC patients. Amplification 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, respectively). Conclusions We conclude that the persistent amplification and overexpression of CBP in ERα- and PR-positive BC highlights the significance of CBP as a new diagnostic marker and therapeutic target in hormone-positive BC.

Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy

“…A previous study showed that PGC-1α levels were higher in the HER2+ and the basal subtypes than in other subtypes, which also showed poor prognosis in both subtypes [ 112 ]. CREBBP amplification occurs in ER+ and TNBC but not in HER2+ subtypes [ 113 ]. Recently, CREBBP was identified as a novel driver of TNBC progression [ 114 ].…”

Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: Does sequence matter?

“…The protein was quantified using the DC ™ protein assay kit (Bio-Rad, United States) and Western blot was performed as described previously (Ramadan et al, 2021). The samples containing equal amounts of protein (15-30 μg) were loaded into the gels to be separated on either 8% or 12% SDS polyacrylamide gel and transblotted onto the nitrocellulose membrane (Bio-Rad, United States).…”

Effect of Safranal On The Response Of Cancer Cells To Topoisomerase I Inhibitors: Dose Sequence Matter?

“…To study the expression of various protein markers, cells were seeded, treated as mentioned in the comet assay and the total cell lysate was obtained by incubation with lysis buffer (Glycerol, 20% SDS & 1 M Tris, pH 6.8) containing protease inhibitor cocktail (Sigma-Aldrich, USA). Protein was quanti ed using DC TM protein assay kit (Bio-Rad, USA) and Western blot was performed as described previously by Ramadan et al, 2021 [29]. Samples containing equal amounts of protein (15-30 µg) were loaded into the gels to be separated on either 8% or 12% SDS polyacrylamide gel and transblotted onto nitrocellulose membrane (Bio-Rad, USA).…”