Roles of the Transcription Factors Snail and Slug During Mammary Morphogenesis and Breast Carcinoma Progression

Abstract

The zinc-finger transcription factors Snail and Slug are involved in different processes controlling cell differentiation and apoptosis. They also appear to be involved in tumor progression. Their putative involvement in mammary gland development has not been specifically examined so far. Slug is expressed at a significant level in normal breast, and indirect evidence suggests it could be implicated in tubulogenesis. As an antiapoptotic agent, it could also protect epithelial cells from death during ductal lumen formation and during breast involution. In breast carcinomas, Snail transcription factors have been linked to tumor progression and invasiveness. Possible mechanisms include repression of the E-cadherin gene by Snail or Slug. However, it is not clear how this transcriptional activity is implicated in vivo. Other possible mechanisms involve maintenance of a plastic phenotype by Slug that could participate in local invasion of ductal carcinomas, and interference with apoptotic pathways that could contribute to global tumor growth and radioresistance. These processes probably also involve interactions with estrogen, EGF, or c-kit pathways.