Aberrant Ret expression impacts in normal mammary gland post-lactation transition enhancing cancer potential

Ret is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors described as oncogenes in the breast have been shown to participate in specific developmental stages. We discover that Ret is present in lactation and its expression dramatically decreases in the following period named involution. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of Ret in the mammary epithelium during post-lactation transition to involution is accompanied by tissue remodeling defects enhancing cancer potential. Mechanistically, using the Ret/MTB mouse we show by RNA-seq that Ret overexpression during lactation promotes a signature of priming involution, including Stat3 activation.