Linda Schuler

Prolactin exposure has been epidemiologically linked to elevated risk for aggressive ERα+ breast cancer.  Anti-estrogen resistant metastatic ERα+ cancers account for the majority of breast cancer deaths.  The Schuler laboratory uses preclinical models to examine the role of prolactin in the developing pathology of metastatic ERα+ breast cancer, and its crosstalk with estrogen, growth factors, and properties of the extracellular matrix in tumor behavior and therapeutic responsiveness.  Using the NRL-PRL transgenic mouse, which elevates prolactin locally in the mammary gland, they have shown that prolactin can powerfully influence the epithelial hierarchy and transcriptional regulatory programs in the absence of estrogen and progesterone, resulting in increased progenitor/stem cell populations.  Prolactin can also temper the actions of ovarian steroids, opposing steroid-driven luminal maturation.   Together, these actions begin to explain its role in development of breast cancer.   The ERα+ cancers that develop in the NRL-PRL mouse can be serially transplanted to syngeneic recipients, providing a model to examine cancer stem cells and responses to anti-estrogens and other adjuvant therapies.  Recent investigations have revealed that anti-estrogens can raise cancer stem cell activity in the absence of effects on growth, and that primary tumors and lung metastases display activation of different signaling pathways and responses to therapies.  These studies are illuminating the biology of luminal B cancers, and will facilitate development of prevention and treatment strategies.

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