The transcriptional coactivator Amplified in Breast Cancer 1 (AIB1) plays a major role in the progression of hormone and HER2-dependent breast cancers but its role in triple negative breast cancer (TNBC) is undefined.
Amplified in breast cancer 1 (AIB1) is a candidate oncogene in human breast cancer, which has been identified to be amplified and overexpressed in several types of other human cancers.
Although it was found that AIB1 could be phosphorylated by some kinases including PI3K, the function of AIB1 and AKT interaction in breast cancer is not well defined.
Furthermore, <i>in vivo</i> syngeneic tumor studies revealed that PELP1 knockdown resulted in increased survival of tumor-bearing mice as compared with mice injected with control cells.<b>Implications:</b> These data demonstrate that cytoplasmic PELP1/AIB1-containing complexes function to promote advanced cancer phenotypes, including outgrowth of stem-like cells, associated with estrogen-independent breast cancer progression.<i></i>.
AIB1 was analyzed with immunohistochemistry in tissue microarrays of the Danish subcohort (N = 1396) of the International Breast Cancer Study Group's trial BIG 1-98 (randomization between adjuvant tamoxifen versus letrozole versus the sequence of the two drugs).
Progestin and antiprogestin responsiveness in breast cancer is driven by the PRA/PRB ratio via AIB1 or SMRT recruitment to the CCND1 and MYC promoters.
AIB1 reduction in MCFDCIS cells was correlated with significant reduction in the CD24-/CD44+ breast cancer-initiating cell (BCIC) population, and a decrease in myoepithelial progenitor cells in the DCIS lesions in vitro and in vivo.
ANCO1 can also repress other E2-responsive genes, indicating that AIB1, AIB1-Δ4 and ANCO1 are important determinants of endocrine and growth factor responsiveness in breast cancer.
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.
Studies were included in the meta-analysis if they met all the predetermined criteria, such as: (a) case-control or cohort studies; (b) the primary outcome was clearly defined as BC; (c) the exposure of interest measured was AIB1 polyglutamine repeat length genotype; (d) provided relative risk (RR) or odds ratio (OR) estimates and their 95% confidence intervals (CIs).
This study establishes a role for AIB1 in AI-resistant breast cancer and describes a new mechanism of ERα/AIB1 gene regulation which could contribute to the development of an aggressive tumor phenotype.
AIB1 is frequently overexpressed in breast cancer and has functions that promote oncogenesis that are independent of estrogen receptor (ER) coactivation.
The nuclear receptor and bona fide oncogene, steroid receptor coactivator-3 (SRC-3, AIB1), acts as a master transcriptional regulator of breast cancer by transducing growth signals via the estrogen receptor alpha (ER).