Premium
Annexin‐1 signals mitogen‐stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2
Author(s) -
Khau Thippadey,
Langenbach Shenna Y.,
Schuliga Michael,
Harris Trudi,
Johnstone Cameron N.,
Anderson Robin L.,
Stewart Alastair G.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-154096
Subject(s) - annexin a1 , annexin , protein kinase b , cell growth , small interfering rna , pi3k/akt/mtor pathway , chemistry , estrogen receptor , stromal cell , microbiology and biotechnology , cancer research , biology , signal transduction , cell , cell culture , medicine , biochemistry , cancer , transfection , breast cancer , genetics
The role of the calcium‐ and phospho‐lipid‐binding protein annexin I (ANXA1) in cell cycle regulation has been investigated in estrogen receptor (ER)‐positive MCF‐7 and ER‐negative MDA‐MB‐231 breast tumor cell lines. In MCF‐7 cells, ANXA1‐targeting small interfering RNA (siRNA) reduced ANXA1 mRNA and protein levels and attenuated cell proliferation induced by FCS, estradiol, or epidermal growth factor. Well‐characterized agonists for the known ANXA1 receptor, FPR2, including the ANXA1 N‐terminal proteolytic product ANXA1 2 _ 26 , lipoxin A 4 (LXA 4 ), and the synthetic peptide, Trp‐Lys‐Tyr‐Met‐Val‐D‐Met (WKYMVm), stimulated proliferation of MCF‐7 and MDA‐MB‐231 cells that was attenuated by incubation with FPR2 antagonists WRW 4 (1 µM) or Boc2 (100 nM) or by siRNA against FPR2. FCS‐induced mitogenic responses were attenuated by each of the FPR antagonists and by siRNAagainst FPR2 and, to a lesser extent, FPR1. LXA 4 increased phosphorylation of Akt, p70 S6K but not ERK1/2. Increases in cyclin D1 protein induced by FCS or LXA 4 were blocked by the PI3 kinase inhibitor, LY294002, and attenuated by FPR2 antagonism using Boc2. In invasive breast cancer, immunohis‐tochemistry revealed the presence of ANXA1 and its receptor, FPR2, in both tumor epithelium and stromal cells. These observations suggest a novel signaling role for ANXA1 in mitogen‐activated proliferation of breast tumor epithelial cells that is mediated via activation of FPR1 and FPR2.—Khau, T., Langenbach, S. Y., Schu‐liga, M., Harris, T., Johnstone, C. N., Anderson, R. L., Stewart, A. G. Annexin‐1 signals mitogen‐stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2. FASEB J. 25, 483_496 (2011). www.fasebj.org