Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death—metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed. J. Cell. Physiol. 213: 374–383, 2007.

MYB (the human ortholog of c- myb ) is expressed in a high proportion of human breast tumors, and that expression correlates strongly with estrogen receptor (ER) positivity. This may reflect the fact that MYB is a target of estrogen/ER signaling. Because in many cases MYB expression appears to be regulated by transcriptional attenuation or pausing in the first intron, we first investigated whether this mechanism was involved in estrogen/ER modulation of MYB . We found that this was the case and that estrogen acted directly to relieve attenuation due to sequences within the first intron, specifically, a region potentially capable of forming a stem–loop structure in the transcript and an adjacent poly(dT) tract. Secondly, given the involvement of MYB in hematopoietic and colon tumors, we also asked whether MYB was required for the proliferation of breast cancer cells. We found that proliferation of ER ⁺ but not ER ⁻ breast cancer cell lines was inhibited when MYB expression was suppressed by using either antisense oligonucleotides or RNA interference. Our results show that MYB is an effector of estrogen/ER signaling and provide demonstration of a functional role of MYB in breast cancer.