The mechanisms through which opioids regulate the activity of malignant breast epithelial cells are currently unknown. In the present study we report the differential actin cytoskeleton reorganization induced by opioids in malignant (MCF7) and nonmalignant ( @entity1 ) breast epithelial cells expressing functional opioid receptors. Exposure of MCF7 cells to the opioid agonist alpha(s1) casomorphin induced important actin assembly and reorganization, including the formation of filopodia and lamellipodia. In contrast, incubation of @entity1 cells with alpha(s1) casomorphin revealed a partial but transient disassembly of actin microfilaments. Immunoprecipitation and immunoblot analyses showed rapid phosphorylation of @entity3818 ( @entity3818 ) and @entity10274 in opioid-treated MCF7 cells. Moreover, @entity3818 associates with @entity4357 -3 (PI-3 kinase), the latter being subsequently phosphorylated and activated. In addition, a substantial activation of the small GTPase @entity5180 was observed. Pretreatment of MCF7 cells with the specific PI-3 kinase inhibitor @entity2307 abolished both the activation of @entity5180 and actin reorganization, while the opioid-induced phosphorylation of @entity3818 and @entity10274 remained unaffected. Interestingly, in opioid-treated @entity1 cells this signaling cascade remained inactive, while we identified rapid phosphorylation of actin regulating the protein villin. Finally, opioids differentially inhibited cell motility in each cell line. Our data suggest a distinct, opioid-induced, signaling pathway activated in malignant breast epithelial cells, leading to important actin reorganization. These findings may indicate a potential antineoplastic role of opiates, based on the activation of differential signaling mechanisms.

Distinct signaling pathways regulate differential opioid effects on actin cytoskeleton in malignant MCF7 and nonmalignant XXXX @entity1 breast epithelial cells.

@entity1 :: ('9606', 'Species') :: ['MCF12A'] @entity10274 :: ('7414', 'Gene') :: ['vinculin'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity3818 :: ('5747', 'Gene') :: ['FAK', 'focal adhesion kinase'] @entity5180 :: ('5879', 'Gene') :: ['Rac1'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol']
@entity1 :: (9606,Species) :: ['MCF12A']
