Gene expression profiling of ErbB receptor and ligand-dependent transcription

被引:19
作者
Amin, DN
Perkins, AS
Stern, DF
机构
[1] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
关键词
ErbB; HER-2; breast cancer; microarray; immediate early genes;
D O I
10.1038/sj.onc.1207257
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Overexpression of ErbB2 and ErbB4 receptors in breast cancers may be accompanied by contrasting clinical outcomes. To investigate the molecular mechanisms contributing to these differences, we undertook a comparative study of gene expression regulated by the two receptors. Agonistic antibodies were employed to activate ErbB2 and ErbB4 in isolation from the other ErbBs in breast cancer cells. Gene expression pro. ling using a 16 755-gene oligonucleotide array was performed to identify transcriptional targets of receptor activation. Our results indicate that, in the same cell line, ErbB2 and ErbB4 activation influence gene transcription differentially. Although there are genes that are regulated by signaling from both receptors, there are also receptor-specific targets that are preferentially regulated by each receptor. We further show that two ligands acting via the same receptor homodimer may activate different subsets of genes. Many of the induced genes are hitherto unidentified targets of ErbB signaling. These include ErbB4 targets EPS15R, GATA4, and RAB2 and ErbB2-activated HRY/HES1 and PPAP2A. Targets of ErbB2 homodimer signaling may be especially important as markers in breast cancer, where ErbB2 homodimerization mediated by overexpression and ligand-independent activation is common.
引用
收藏
页码:1428 / 1438
页数:11
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