Bautista S, Vallès H, Walker R L, Anzick S, Zeillinger R, Meltzer P, Theillet C
Equipe Génome et Cancer UMR 5535 Centre National de la Recherche Scientifique, Centre de Recherche, Montpellier, France.
Clin Cancer Res. 1998 Dec;4(12):2925-9.
The AIB1 gene was isolated upon microdissection of the homogeneously staining regions observed in breast cancer cell lines. It was subsequently shown to map at a region at 20q12 that is frequently amplified in breast tumors. In a screen of breast tumor cell lines, of all the genes mapping to the region, AIB1 appeared to be the most consistently amplified and overexpressed. AIB1 shares homology with the SRC-1 family of nuclear receptor coactivators. It was found to interact in a ligand-dependent manner with the estrogen receptor (ER) and to result in increased levels of estrogen-dependent transcription. These properties could be of important biological significance in breast and ovarian cancerigenesis, and we were, therefore, interested in determining whether the amplification of the AIB1 gene was associated with a particular phenotype or subgroup in these tumors. We tested a population of 1157 breast and 122 ovarian tumors in which DNA amplification had been determined previously at 15 chromosomal locations. Amplification of the AIB1 gene was observed in 4.8% of breast cancers and 7.4% of ovarian cancers. In breast tumors, AIB1 was correlated with ER and progesterone receptor positivity, as well as with tumor size. Correlation was also observed with the amplification of MDM2 and FGFR1 genes, but interestingly, no correlation was found with the amplification of CCND1, which is known to be strongly associated with ER. Furthermore, analyzing at 20q12-q13 range, we show the existence of three amplification cores, represented by AIB3/AIB4, AIB1, and RMC20C001. AIB1 and CCND1 amplifications may, thus, represent two different subsets of ER-positive breast tumors.
AIB1基因是在对乳腺癌细胞系中观察到的均匀染色区进行显微切割后分离得到的。随后发现它定位于20q12区域，该区域在乳腺肿瘤中经常发生扩增。在对乳腺肿瘤细胞系的筛查中，在所有定位于该区域的基因中，AIB1似乎是扩增和过表达最一致的。AIB1与核受体共激活因子的SRC-1家族具有同源性。发现它以配体依赖的方式与雌激素受体（ER）相互作用，并导致雌激素依赖转录水平升高。这些特性在乳腺癌和卵巢癌发生过程中可能具有重要的生物学意义，因此，我们有兴趣确定AIB1基因的扩增是否与这些肿瘤中的特定表型或亚组相关。我们检测了1157例乳腺癌和122例卵巢癌患者，这些患者先前已确定了15个染色体位置的DNA扩增情况。在4.8%的乳腺癌和7.4%的卵巢癌中观察到AIB1基因的扩增。在乳腺肿瘤中，AIB1与ER和孕激素受体阳性以及肿瘤大小相关。还观察到与MDM2和FGFR1基因的扩增相关，但有趣的是，与已知与ER密切相关的CCND1的扩增没有相关性。此外，在20q12-q13范围内进行分析时，我们发现存在三个扩增核心，分别由AIB3/AIB4、AIB1和RMC20C001代表。因此，AIB1和CCND1的扩增可能代表ER阳性乳腺肿瘤的两个不同亚组。
