Researchers from the group of Transformation and Metastasis from the Institute of Biomedical Research of Bellvitge (IDIBELL) led by Eva Gonzalez Suarez have discovered a dual function of RANK protein in the differentiation of mammary alveoli and lactogenesis. The results were published in the Stem Cells journal.
Until now, a positive role for RANK in alveogenesis (differentiation of mammary alveoli) was described during early pregnancy. “What we have seen,” explains the researcher Eva Gonzalez-Suarez “is that in later stages of pregnancy RANK plays a negative role: it inhibits the action of prolactin, preventing phosphorylation of Stat5, lactogenesis and milk secretion”
Through gene expression analysis, researchers have shown that activation of the RANK pathway at midgestation prevents the differentiation of alveolar cells to milk secreting cells not only in genetically modified mouse models (with high levels of expression of RANK) but also in wild-type mouse models (without genetic modification). Moreover, upon pharmacologically inhibition of RANKL at midgestation in wild type mice, an exacerbated and early lactogenesis occurs.
“These results explain, at the molecular level, the fact that both the absence and the overactivation of RANK interfere with lactation,” explains Gonzalez-Suarez. She adds that “it is clear that a strict regulation of RANK signaling pathway is required for proper mammary gland differentiation.”
A Cordero*, P Pellegrini*, A Sanz-Moreno , EM Trinidad, J Serra-Musach J, C Deshpande, WC Dougall, MA Pujana and E González Suarez. Rankl impairs lactogenic differentiation through inhibition of the prolactin/Stat5 pathway at midgestation. Stem Cells, in press. * contributed equally