The Role of PEA3 in Mammary Gland Development and Tumorigenesis

Abstract

<p> PEA3 is a member of the ets family of transcription factors. It is expressed throughout embryonic development and in mouse mammary adenocarcinomas induced by expression of the receptor tyrosine kinase Neu. Mice lacking PEA3 due to a targeted disruption of the gene, develop normally, however, male mice fail to mate for yet undetermined reasons. To further understand the role of PEA3 in mammary gland development and tumorigenesis, the effects of loss of function of PEA3 were examined in tumor formation and in mammary gland development. </p> <p> Analysis of tumor formation in PEA3 +I+ and PEA3 -/-animals failed to show a statistically significant difference in tumor onset. Loss of PEA3 did not affect the tumor morphology, nor did it inhibit metastasis of these tumors to the lung. These data indicate that PEA3 is not required for tumor formation or metastasis. </p> <p> PEA3 deficient animals displayed defects in branching morphogenesis in the mammary gland. Decreased ductal branching was observed in virgin and pregnant females. Mice with decreased levels of PEA3 expression also exhibited defects in branching morphogenesis, indicating a dosage effect. PEA3 is expressed in the myoepithelial cells during puberty and pregnancy. It is also express in the highly proliferative cap cell layer of the terminal end bud. In the embryonic mammary gland, PEA3 is expressed as early as 10.5 days in the mammary epithelium and continues late in embryogenesis. Expression in the male mammary gland is lost at approximately embryonic day 16. </p>