PEA3 is the founding member of a subfamily of closely related Ets transcriptional regulatory proteins that includes ERM and ER81. The PEA3 subfamily members share greater than 95% identity in their ETS DNA binding domain and 500/o sequence similarity overall, suggesting these genes may serve redundant functions. The overexpression of each member is positively correlated with HER2 mediated breast tumorigenesis in humans and mice, suggesting a role for this subfamily in mammary development and oncogenesis. This study first addresses the role of PEA3 in cellular transformation mediated by oncogenic Ras and Neu. Wildtype and PEA3-null mouse embryo fibroblast cell lines were infected and tested for focus formation. PEA3-null fibroblasts are refractory to transformation as compared to their wildtype counterparts. Ras and Neu transformed foci show elevated PEA3 subfamily mRNA transcripts and PEA3 protein. ERM and ER81 are expressed in PEA3-null fibroblasts and do not appear to compensate for loss of function mutations in the PEA3 gene resulting in the transformation-defective phenotype. Expression of candidate PEA3 target genes (MMP-3 and MMP-9, which have known roles in transformation) is compromised in PEA3-null fibroblasts. Re-expression of PEA3 in these cells rescues the transformation-deficient phenotype and restores expression of MMP-3 and MMP-9. Hence, PEA3 appears to be a crucial effector in Ras and Neu mediated transformation, in addition to serving an important regulatory role of genes involved in cell motility and invasive tumor behaviour. This study also addresses the role of ER81 in normal mammary gland development. PEA3 is required for normal mammary gland development, as displayed by the reduced branching phenotype in PEA3-null female mice. Mice lacking functional ER81 were generated to determine if ER81 serves a similar role in mammary gland development. ER81 is expressed in the epithelial cells of mammary buds at E 1 0.5, when these structures first appear during mouse embryogenesis. ER81 is then differentially expressed during postnatal mammary gland development, with highest expression occurring at times of extensive epithelial branching. During puberty, expression is observed in undifferentiated cap and body cells of terminal end buds, in differentiated luminal and myoepithelial cells of ducts. During pregnancy, expression in luminal epithelial cells is lost, but persists in the myoepithelial cells within the ducts and alveoli. Targeted disruption of both ERSt alleles result in severely runted mice that die by 4 weeks of age, thereby precluding study of mammary gland development in these mice beyond this developmental stage. However, loss of a single ER81 allele results in healthy looking mice, comparable in size and lifespan to wildtype littermates. Studies employing ER81 heterozygous mice reveal a 50% allelic dose is sufficient for normal mammary gland development. Loss of a single ER81 allele did not result in any overt phenotypes in ductal branching, lobulo-alveolar development, or morphology of the surrounding fat pad. / Thesis / Master of Science (MSc)