Sustained Ret expression during mammary gland post-lactation induces premature involution enhancing tumorigenesis

SABRINA A. VALLONE; MARTÍN GARCÍA SOLÁ; ROBERTO P. MEISS; ROBERT D. CARDIFF; LEWIS A. CHODOSH; NANCY E. HYNES; CAROLINA SCHERE-LEVY; EDITH C KORDON.; ALBANA GATTELLI

Congreso; SAIC 2019; 2019

Ret is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors described as oncogenes have been shown to play important roles during normal mammary gland development. We found that Ret is normally expressed in lactation and its deregulation alters the efficient transition to involution. Involution is the period which returns the lactating gland to a quiescent state after weaning (post-lactation stage). Inhibition of Ret activity in vivo does not alter lactation, however impacts in the involution process. Nevertheless, Ret overexpression promotes factors that drive involution, including premature Stat3 activation. In addition, sustained expression of Ret during the post-lactation produces defective cell recycling and enhances cancer potential disrupting Stat3 signaling through SOCS3, a key regulator of Stat pathway. These data demonstrate that Ret has a key role in mammary gland post-lactation stage.