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CXCR4 Activation Induces Epidermal Growth Factor Receptor Transactivation in an Ovarian Cancer Cell Line
Author(s) -
PORCILE CAROLA,
BAJETTO ADRIANA,
BARBERO SIMONE,
PIRANI PAOLO,
SCHETTINI GENNARO
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.021
Subject(s) - cancer research , ovarian cancer , transactivation , mapk/erk pathway , epidermal growth factor receptor , epidermal growth factor , cxc chemokine receptors , biology , cxcl14 , microbiology and biotechnology , signal transduction , chemokine receptor , chemistry , receptor , cancer , chemokine , biochemistry , gene expression , gene , genetics
A bstract : Chemokines are a family of proteins that have pleiotropic biological effects. They are well known to regulate the recruitment and trafficking of leukocytes to sites of inflammation. Chemokines are grouped into four classes based on the positions of key cysteine residues: C, CC, CXC, and CX3C. Stromal cell‐derived factor‐1 (SDF‐1), the ligand of the CXCR4 receptor, is a CXC chemokine and is a highly conserved gene. Ovarian cancer typically disseminates widely in the abdomen, a characteristic that limits curative therapy. The mechanisms that promote ovarian cancer proliferation are incompletely understood. We studied a human ovarian adenocarcinoma cell line (OC 314) and investigated the role of CXCR4 activation by SDF‐1 in human ovarian cancer. We demonstrate that CXCR4 and SDF‐1 mRNA are expressed in OC 314. We show that SDF‐1α induces proliferation in ovarian cancer cells in a dose‐dependent manner. Moreover, we demonstrate that the SDF‐1‐dependent proliferation correlates to the phosphorylation and activation of extracellular signal‐regulated kinases (ERK)1/2, which in turn are correlated to epidermal growth factor (EGF) receptor transactivation. In fact, AG1478, a specific inhibitor of the EGF receptor kinase, blocked both SDF‐1α‐dependent proliferation and ERK1/2 activation.