The RhoA-Rok-myosin II pathway is involved in extracellular matrix-mediated regulation of prolactin signaling in mammary epithelial cells.
Bottom Line: Under these culture conditions, the RhoA pathway is activated, leading to downregulation of prolactin receptor expression and reduced prolactin signaling.In addition, inhibition of myosin II ATPase activity by blebbistatin also exerts a beneficial effect on prolactin receptor expression and prolactin signaling, suggesting that tension exerted by the collagen substratum, in collaboration with the RhoA-Rok-myosin II pathway, contributes to the failure of prolactin signaling.They display high levels of RhoA activity and are inefficient in prolactin signaling, stressing the importance of matrix stiffness in signal transduction.
Affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.Show MeSH
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Mentions: Since RhoA inhibits insulin signaling in MECs, we reasoned that it might have a similar effect on prolactin signaling, either at the level of prolactin receptor expression or further downstream. We therefore expressed constitutively active RhoA (L63RhoA) in MECs cultured on BM. This diminished the expression of prolactin receptor, and completely prevented prolactin-induced Stat5 tyrosine phosphorylation and β-casein expression (Fig. 3). To confirm that RhoA-mediated inhibition of prolactin signaling is not secondary to the induction of apoptosis, ZVAD-fmk was added to the cultures to prevent caspase activation. ZVAD-fmk did not eliminate the inhibitory effect of RhoA on β-casein expression (Fig. 3). Thus, RhoA activation prevents prolactin receptor expression and Stat5 signaling.
Affiliation: Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, ROC.