A functional and regulatory network associated with PIP expression in human breast cancer.

<h4>Background</h4>The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted co...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Marie-Anne Debily, Sandrine El Marhomy, Virginie Boulanger, Eric Eveno, Régine Mariage-Samson, Alessandra Camarca, Charles Auffray, Dominique Piatier-Tonneau, Sandrine Imbeaud
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2009
Materias:
R
Q
Acceso en línea:https://doaj.org/article/49cd927f14db420e84bfb7dc6d834b96
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:<h4>Background</h4>The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes.<h4>Principal findings</h4>Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP-] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters.<h4>Conclusions</h4>Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator.