Abstract
BackgroundAIB1 (amplified in breast cancer I) is a member of the p160 steroid receptor coactivator family. AIB1 is frequently overexpressed in breast cancer and has functions that promote oncogenesis that are independent of estrogen receptor (ER) coactivation. We investigated prognostic significance of AIB1 and relationship between AIB1 and ER, progesterone receptor (PR), androgen receptor (AR), DAX-1, and HER2.MethodsRNA in situ hybridization (ISH) and immunohistochemical (IHC) staining for AIB1, IHC staining for ER and the progesterone receptor (PR) and IHC staining and silver in situ hybridization (SISH) for HER2 were performed for 185 breast cancer cases.ResultsA high level of expression of AIB1 mRNA was observed in 60.0% of tumors. IHC analysis detected AIB1 positivity in 47.3% of tumors, which did not correlate with AIB1 mRNA expression (p = 0.24, r = 0.10). AIB1 protein expression correlated with AR and DAX-1 expression (p = 0.01, r = 0.22 and p = 0.02, r = 0.21, respectively) but not with ER or PR expression (p = 0.14, r = -0.13 and p = 0.16, r = -0.12, respectively). AIB1 protein expression correlated with the amplification of the HER2 gene (p = 0.03, r = 0.19). In contrast to AIB1 protein expression, AIB1 mRNA expression did not correlate with AR, DAX-1, ER, and PR expression, and the amplification of the HER2 gene (p > 0.05 for all).There were trends that strong AIB1 protein expression correlated with poorer disease free survival (p = 0.07). Strong AIB1 protein expression correlated with poorer overall survival (p = 0.04). Among the ER-negative subgroup, strong AIB1 protein expression correlated with poorer disease free survival and overall survival (p = 0.01 and p < 0.01, respectively).ConclusionsStrong AIB1 protein expression was poor prognostic factor in breast cancer, especially in ER-negative breast cancers. Further investigation is essential to determine whether AIB1 might be effective therapeutic targets for ER-negative breast cancers.
Highlights
amplified in breast cancer 1 (AIB1) is a member of the p160 steroid receptor coactivator family
Using a cut-off value equal to the AIB1 mRNA in normal breast tissues (1+), we determined that 60.0% of tumors had low levels (0 and 1+) of AIB1 mRNA expression and 40.0% of tumors had high levels (2+ and 3+)
AIB1 protein expression correlated with androgen receptor (AR) and DAX-1 expression
Summary
AIB1 (amplified in breast cancer I) is a member of the p160 steroid receptor coactivator family. AIB1 is frequently overexpressed in breast cancer and has functions that promote oncogenesis that are independent of estrogen receptor (ER) coactivation. Estrogen signaling are the interactions of ER with transcriptional coactivators including p/CAF, CREB binding protein(CBP), p300 and the p160 family members [3]. AIB1 (amplified in breast cancer I) is a member of the p160 steroid receptor coactivator family, which includes SRC-1 and SRC-2 [4]. It is located on chromosome 20q12, a common region of amplication in breast cancer. AIB1 is a preferred co-activator for AR in prostate cancer [9]
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