title: Cyclooxygenase-2 utilizes Jun N-terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells.
abstract: Elevated cyclooxygenase-2 (COX-2) expression in breast tumors is associated with a lower survival rate in patients with estrogen receptor α (ERα)-positive tumors. We hypothesized that COX-2 reduces the survival rate of breast cancer patients with ERα-positive tumors since COX-2 increases the invasiveness of ERα-positive breast tumors and decreases tumor sensitivity to tamoxifen. Previously, we demonstrated that COX-2 stimulates the activity of protein kinase C (PKC) to increase the invasiveness of ERα-positive MCF-7 breast cancer cells and to decrease the sensitivity of MCF-7 cells to tamoxifen. High levels of COX-2 are associated with the activation of the mitogen-activated protein kinase (MAPK) family and the Akt kinase. However, it is not known whether these kinases mediate COX-2-induced invasive activity and tamoxifen resistance. In the present study, we report that COX-2 utilizes PKC to enhance the phosphorylation of Jun N-terminal kinases (JNKs), but not that of other MAPK family members or Akt. Inhibition aimed at JNKs reduced COX-2-induced invasion but not COX-2-induced tamoxifen resistance. We conclude that JNKs are essential for induced cell invasion by COX-2, but not tamoxifen resistance, in ERα-positive breast cancer cells.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, University of Nuevo Leon, San Nicolas de los Garza, Nuevo León, Mexico.
authors.forename: Vianey
authors.initials: V
authors.lastname: Gonzalez-Villasana
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Gutiérrez-Puente
authors.forename: Ana M
authors.initials: AM
authors.lastname: Tari
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004338:Drug Combinations; D007797:Laminin; D009687:Nuclear Proteins; D011509:Proteoglycans; D013629:Tamoxifen; C059485:matrigel; D003094:Collagen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases