Carcinogenesis Advance Access published online on November 21, 2003
Carcinogenesis, doi:10.1093/carcin/bgh024
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Laboratoire d'Oncogénétique - INSERM E0017, Centre Rene Huguenin, St-Cloud, France; Laboratoire de Génétique Moléculaire - UPRES EA 3618, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes - Paris V, Paris, France
* Corresponding author. E-mail: i.bieche{at}stcloud-huguenin.org.
Received 12 February 2003
; revised 4 August 2003
; accepted 29 October 2003
The PEA3/E1AF/ETV4 gene encodes an Ets-related transcription factor that is expressed in the epithelial cells of the mammary gland. Previous reports have shown that PEA3 can upregulate promoter activities of many genes associated with tumorigenesis. A significant fraction of those encode matrix metalloproteinases (MMP genes) required for degradation of the extracellular matrix. To better obtain a molecular characterization of PEA3 expression in sporadic breast cancer, we quantified PEA3 mRNA by means of real-time RT-PCR assay in a large series of human primary breast tumors. PEA3 expression showed wide variations in tumor tissues, being underexpressed in 30/130 (23.1%) and overexpressed in 18/130 (13.8%) compared to normal breast tissues. High PEA3 mRNA levels correlated significantly with SBR histopathological grade III (P = 0.018) but not with poor prognosis, suggesting that PEA3 is a marker of tumor aggressiveness rather than a prognostic factor in human breast cancer. We also observed positive links between the expression of PEA3 and those of MKI67 and ERBB2 (P = 0.034 and P = 0.045, respectively) and an inverse relationship with ER Our results also suggest major roles of the MMP2, NRG1 and CGB genes (which encode type I gelatinase, heregulin and human chorionic gonadotropin Taken together, these data confirms the role of the PEA3 gene in breast tumorigenesis, and suggest the existence of numerous other still unknown genes transactivated by the PEA3 transcription factor.
Breast cancer, Gene expression, Real-time RT-PCR, PEA3
Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast tumors: positive links to MMP2, NRG1 and CGB expressions
2 Laboratoire d'Oncogénétique - INSERM E0017, Centre Rene Huguenin, St-Cloud, France
3 Laboratoire de Génétique Moléculaire - UPRES EA 3618, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes - Paris V, Paris, France
(P = 0.0016). Our results do not support recent findings suggesting that PEA3 could be a tumor-suppressor gene that can act therapeutically in ERBB2 overexpressed tumors.
subunit, respectively) in the PEA3 pathway dysregulation observed in breast cancer.
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