Gene expression profiling of ErbB receptor and ligand-dependent transcription.
Oncogene
; 23(7): 1428-38, 2004 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-14973552
ABSTRACT
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 profiling 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Regulação Neoplásica da Expressão Gênica
/
Receptor ErbB-2
/
Receptores ErbB
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article