Amplified in breast cancer 1
(AIB1)

Activator of thyroid and retinoic acid receptor (ACTR) (Chen H. et al., 1997)
Receptor-associated coactivator 3 (RAC3) (Li H. et al., 1997)
Thyroid hormone receptor activator molecule 1 (TRAM-1) (Takeshita A. et al., 1997)
Steroid receptor coactivator-3 (SRC-3) (Suen C.S. et al., 1998)
p300/CBP cointegrator associate protein (p/CIP) (Torchia J. et al., 1997)
Nuclear receptor coactivator-3 (NCoA-3)

Gene: maps to 20q12. Amplification of chromosome 20q is frequent but complex in breast cancer. It involves several distinct variably coamplified chromosomal segments derived from 20q11, 20q12, and 20q13.
mRNA: size: 9.1 kb (Anzick S.L. et al., 1997).
Protein: AIB1 belongs to the SRC-1 family of nuclear receptor coactivators and was shown to interact at the protein level with ER in a ligand-dependent manner. In transient transfection assays, its overexpression resulted in increased levels of estrogen-dependent transcription (Anzick S.L. et al., 1997).

AIB1 maps to the long arm of chromosome 20, one of the most recurrent sites (along with 1q, 8q, and 17q) of DNA copy gains in breast cancers (up to 18% of primary tumors and 40% of cell lines).

Cell lines:
- Amplification of AIB1 gene and incresed expression of AIB1 mRNA were found in MCF-7 and BT-474 breast cancer cell (BCC) lines (Guan X.Y. et al., 1996).

- By fluorescence in situ hybridization (FISH), high-level amplification of AIB1 (>20-fold) was observed in three ER-alpha-positive BCC lines: BT-474, MCF-7, and ZR-75-1. This amplification was not observed in another ER-alpha-positive (T-47D) and in six ER-alpha-negative (MDA-MB-361, -436, -468, -453, BT-20, and UACC-812) BCC lines. In ZR-75-1 BCC, amplification of AIB1 (which maps to 20q12) has occurred independently of both the 20q11 and 20q13 regions. By Northern blot analysis, high AIB1 mRNA levels were found in BT-474, MCF-7, and ZR-75-1 BCC lines, (Anzick S.L. et al., 1997).

Tumors:
- By FISH analysis, AIB1 amplification was found in 10/105 specimens of unselected primary breast tumors. The amplification levels were not as high as in the cell lines BT-474, MCF-7, and ZR-75-1. By Northern blot analysis, high AIB1 mRNA levels were found in the 10 breast tumors with amplified AIB1 (Anzick S.L. et al., 1997).

- In a series of 1157 breast tumors, amplification of the AIB1 gene was observed in 4.8% of cases. AIB1 was correlated with estrogen receptor and progesterone receptor positivity. There was also a correlation between the amplifications of AIB1, on one hand, and MDM2 (mapping at 12q13) and FGFR1 (at 8p12), on the other hand. No correlation was found with the amplification of CCND1 (at 11q13), which is known to be strongly associated with ER. AIB1 and CCND1 amplifications could represent two different subsets of ER-positive breast tumors (Bautista S. et al., 1998)

Anzick S.L. et al. (1997) AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965-968.
Bautista S. et al. (1998) In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity. Clin. Cancer Res. 4, 2925-2929.
Chen H. et al. (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with PCAF and CBP/p300. Cell 90, 569-580.
Guan X.Y. et al. (1996) Hybrid selection of transcribed sequences from microdissected DNA: isolation of genes within amplified region at 20q11-q13.2 in breast cancer. Cancer Res. 56, 3446-3450.
Li H. et al. (1997) RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2. Proc. Natl. Acad. Sci. USA 94, 8479-8484.
Suen C.S. et al. (1998) A transcriptional coactivator, steroid receptor coactivator-3, selectively augments steroid receptor transcriptional activity. J. Biol. Chem. 273, 27645-27653.
Takeshita A. et al. (1997) TRAM-1, a novel 160-kDa thyroid hormonr receptor activator molecule exhibits distinct properties from steroid receptor coactivator-1. J. Biol. Chem. 272, 27629-27634.
Thenot S. et al. (1999) In breast cancer, amplification of the steroid receptor coactivator gene AIB1 is correlated with estrogen and progesterone receptor positivity. Clin. Cancer Res. 4, 2925-2929.
Torchia J. et al. (1997) The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 387, 677-684.

SRC-1, SRC-2