These findings suggest that AIB1 overexpression may impact on breast cancer by a mechanism not wholly dependent on steroid receptor coexpression and which may involve other oncogenic events, such as p53 protein stabilization and HER2/neu overexpression.
A key member of this family is SRC-3, initially found to be amplified and expressed in breast cancer it has subsequent been shown to be expressed in malignant disease arising from a wide range of other organs.
In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26-0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21-0.69, P = 0.0015) with tamoxifen treatment.
As the members of the p160/nuclear receptor co-activator (NCOA) family, NCOA1, NCOA2 and NCOA3 are known to be overexpressed in breast cancer and essentially involved in estrogen-mediated cancer cell proliferation we asked if these proteins are involved in the ERα-mediated transactivation of PLAC1 in breast cancer cells.
Chromatin immunoprecipitation assays in T-47D human breast cancer cells revealed a TCDD-dependent recruitment of AHR, nuclear co-activator 3 (NCoA3) and the transcription factor forkhead box A1 (FOXA1), a key regulator of breast cancer cell signaling, to CCNG2 resulting in increases in CCNG2 mRNA and protein levels.
We show that HER2 signaling promotes breast cancer cell proliferation through regulation of E2F1-driven DNA metabolism and replication genes together with phosphorylation and activity of the transcriptional coactivator SRC-3.
The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently amplified and overexpressed in human breast cancer and has been shown to enhance estrogen-dependent transactivation.
AIB1 is frequently overexpressed in breast cancer and has functions that promote oncogenesis that are independent of estrogen receptor (ER) coactivation.
The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently overexpressed in human breast cancer and has been shown to be associated with tamoxifen resistance.
Importantly, immunohistochemistry analysis indicated that ACTR overexpression is highly correlated with the expression of E2F1 and ANCCA in a cohort of human primary and lymph node-metastasized breast cancer specimens.
We propose that differing activities adopted by ERalpha and AIB1 as a consequence of their interactions with and phosphorylation by CK1delta, particularly AIB1 stabilization, influence the transcriptional activity of ERalpha, and therefore have a role in breast cancer development.
Increases of AIB1 levels in breast cancer cells by amplification and/or overexpression may represent one way to confer estrogen-dependent mitogenic stimulation to breast cancer cells.
We found a positive correlation between the transcripts of ERRalpha and AIB1 (amplified in breast cancer-1), a coactivator overexpressed in breast cancers and associated with resistance to antihormone treatment.
Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome.
Consistent with this finding, the abundance of AIB1-Delta3 mRNA was increased in human breast cancer specimens relative to that in normal breast tissue.
Our data link the SMRT corepressor directly with SRC family coactivators in positive regulation of ERalpha-dependent gene expression and, taken with the positive correlation found for SMRT and SRC-3 in human breast tumors, suggest that SMRT can promote ERalpha- and SRC-3-dependent gene expression in breast cancer.
Given the amplified expression of SRC-3 in breast cancers, the objective of this study was to determine how increasing SRC-3 protein levels are regulated in MCF-7 breast cancer cells.