Mechanisms of Regulation of Cell Fate in Breast Development and Cancer

Abstract

This chapter focuses on the mechanisms of regulation of cell fate in breast development, occurring mainly after birth, as well as in breast cancer. First, we will review how the microenvironment of the breast, as well as external cues, plays a crucial role in mammary gland cell specification and will describe how it has been shown to reprogram non-mammary cells into mammary epithelial cells. Then we will focus on the transcription factors and master regulators which have been established to be determinant for basal (BC) and luminal cell (LC) identity, and will describe the experiments of ectopic expression or loss of function of these transcription factors which demonstrated that they were crucial for cell fate. We will also discuss how master regulators are involved in the fate choice of LCs between estrogen receptor (ER)-positive cells and ER- cells, which will give rise to alveolar cells upon pregnancy and lactation. We will describe how oncogene expression induces reprogramming and change of fate of mammary epithelial cells before tumor appearance, which could be an essential step in tumorigenesis. Finally, we will describe the involvement of master regulators of mammary epithelial cells in breast cancer.

Keywords: Breast cancer; Cell fate; Cell reprogramming; Change of fate; Mammary gland; Master regulators.