Ectopic expression of the ets transcription factor ER81 in transgenic mouse mammary gland enhances both urokinase plasminogen activator and stromelysin-1 transcription.
The PEA3 group members PEA3, ER81 and ERM, which are highly conserved transcription factors from the Ets family, are over-expressed in metastatic mammary tumors. In the current study, we present the characterization of a transgenic mouse strain which over-expresses ER81 in the mammary gland via the long terminal repeat of the mouse mammary tumor virus (LTR-MMTV). Although six genotypically positive transgenic lines were identified, only one expressed the ectopic transcript with an exclusive expression in the lactating and late-pregnancy (18th day) mammary glands. No mammary tumor or mammary deregulation appeared after 2 years of ectopic ER81 expression following lactation. We then sought to identify ER81 target genes, and the urokinase plasminogen activator (uPA) and the stromelysin-1, two enzymes involved in extracellular matrix degradation, were found to be transcriptionally upregulated in lactating mammary glands over-expressing ER81. Since these enzymes are involved in metastasis, this murine model could be further used to enhance mammary cancer metastatic process by crossing these animals with mice carrying non-metastatic mammary tumors. We thus created a transgenic mouse model permitting the over-expression of a functionally active Ets transcription factor in the mammary gland without perturbing its development.
Netzer
Sonia
S
UMR 8526 CNRS, Institut de Biologie de Lille, Institut Pasteur de Lille, France.
Leenders
Frauke
F
Dumont
Patrick
P
Baert
Jean-Luc
JL
de Launoit
Yvan
Y
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D004268:DNA-Binding Proteins; C490641:Etv1 protein, mouse; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator; D019278:Matrix Metalloproteinase 3