title: Caveolin-1 regulates EGFR signaling in MCF-7 breast cancer cells and enhances gefitinib-induced tumor cell inhibition.
abstract: Caveolin-1, an essential protein constituent of caveolae, is involved in cell signaling through its association with various signaling molecules. Epidermal growth factor receptor (EGFR) interacts directly with caveolin-1 and this interaction functionally regulates EGFR tyrosine kinase activity. In this report we investigated the role of caveolin-1 overexpression on EGFR signaling in MCF-7 breast cancer cell line. We demonstrate here that although total EGFR expression levels are similar, EGFR phosphorylation is diminished in MCF-7/CAV1 cells compared to parental MCF-7 cells. In addition, MCF-7/CAV1 cells exhibit higher total and activated Akt levels. Moreover, MCF-7/CAV1 cells stimulated with EGF display higher EGFR and Akt phosphorylation associated with enhanced proliferative and motility rates, compared to MCF-7 cells. Pretreatment with gefitinib inhibits EGF-induced stimulation of both EGFR and downstream Akt and MAPK more efficiently in MCF-7/CAV1 than in MCF-7 cells. In accordance, EGF-induced proliferation and migration is more effectively suppressed with gefinitib in MCF-7/CAV1 compared to parental cells. In conclusion these results suggest that caveolin-1 overexpression in MCF-7 breast cancer cell line modulates EGFR activation levels and EGF-induced EGFR signalling. This is associated with enhanced antitumor effects of gefitinib suggesting a role for EGFR inhibition in caveolin-1 overexpressing breast cancers.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Voutes, Greece. georgsec@med.uoc.gr
authors.forename: Sophia
authors.initials: S
authors.lastname: Agelaki
authors.forename: Maria
authors.initials: M
authors.lastname: Spiliotaki
authors.forename: Harris
authors.initials: H
authors.lastname: Markomanolaki
authors.forename: Galatea
authors.initials: G
authors.lastname: Kallergi
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Christos
authors.initials: C
authors.lastname: Stournaras
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D020935:MAP Kinase Signaling System; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; C495540:CAV1 protein, human; D051242:Caveolin 1; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D000077156:Gefitinib