The hormonal control of breast development and breast cancer risk are poorly understood, despite decades of active research. The mammary gland is biologically unique in that mammary gland organogenesis occurs postnatally and is controlled primarily by systemic endocrine factors, making it accessible to detailed study. Clinically, breast cancers are the second leading cause of cancer deaths in women, and the rate of breast cancer occurrence has risen steadily for at least 6 decades. The main hormones that appear to determine breast development are estrogen and prolactin.
We knocked out the prolactin gene of mice and discovered that prolactin is required at a stage of development during which precursor cells for the secretory epithelium differentiate from the ducts, which is a critical determinant of breast cancer risk.
The molecular basis of prolactin action is being investigated using both whole animal and cell culture systems, and in animal and human systems. We have cloned prolactin-regulated genes, the prolactin receptor, and several prolactin-activated transcription factors. One current project is focusing on identifying novel molecular correlates of prolactin-induced mammary development.
Our current focus is on identifying genes that act during the earliest stages of mammary gland differentiation. We have used differential hybridization to gene microarrays and suppression subtractive hybridization cloning to discover gener that are specifically regulated by prolactin during mammary gland development. Our studies have identified novel pathways involving matrix protein kinases and monoamine biosythetic enzymes that mediate prolactin actions on breast development and breast physiology.