EFFECTS OF EPIDERMAL GROWTH-FACTOR (EGF) AND PROLACTIN ON EGF RECEPTOR CYTOSKELETAL ASSOCIATION IN MAMMARY EPITHELIAL-CELLS

Prolactin treatment of NMuMG mammary epithelial cells inhibits the abi lity of epidermal growth factor (EGF) to transduce a variety of signal s, possibly by interfering with receptor tyrosine phosphorylation. How ever, the mechanism by which prolactin inhibits EGF receptor signaling is unclear, The objective of this study was to evaluate the effects o f prolactin on the dynamics of EGF receptor degradation and resynthesi s, and on the association of the receptor with the cytoskeleton. EGF d ecreased the EGF receptor content of NMuMG cells, and this decrease wa s unaffected by prolactin treatment, Subsequent to the decrease in EGF receptors, cells reaccumulated EGF receptors, and this re-accumulatio n was also unaffected by prolactin, In other studies, EGF induced a ra pid association of EGF receptor with Triton X-100-insoluble (cytoskele tal) elements, The cytoskeletally associated receptors were more heavi ly tyrosine phosphorylated than soluble receptors in the absence of pr olactin, In the presence of prolactin, similar amounts of EGF receptor associated with the cytoskeleton, but both cytoskeletal and soluble r eceptors exhibited decreased tyrosine phosphorylation. These studies i ndicate that the effects of prolactin on EGF receptor signaling are no t likely to be due to altered receptor dynamics or cytoskeletal associ ation but are more likely due to an alteration in receptor kinase acti vity.