title: The colony-stimulating factor-1 (CSF-1) receptor sustains ERK1/2 activation and proliferation in breast cancer cell lines.
abstract: Breast cancer is the second leading cause of cancer-related deaths in western countries. Colony-Stimulating Factor-1 (CSF-1) and its receptor (CSF-1R) regulate macrophage and osteoclast production, trophoblast implantation and mammary gland development. The expression of CSF-1R and/or CSF-1 strongly correlates with poor prognosis in several human epithelial tumors, including breast carcinomas. We demonstrate that CSF-1 and CSF-1R are expressed, although at different levels, in 16/17 breast cancer cell lines tested with no differences among molecular subtypes. The role of CSF-1/CSF-1R in the proliferation of breast cancer cells was then studied in MDAMB468 and SKBR3 cells belonging to different subtypes. CSF-1 administration induced ERK1/2 phosphorylation and enhanced cell proliferation in both cell lines. Furthermore, the inhibition of CSF-1/CSF-1R signaling, by CSF-1R siRNA or imatinib treatment, impaired CSF-1 induced ERK1/2 activation and cell proliferation. We also demonstrate that c-Jun, cyclin D1 and c-Myc, known for their involvement in cell proliferation, are downstream CSF-1R in breast cancer cells. The presence of a proliferative CSF-1/CSF-1R autocrine loop involving ERK1/2 was also found. The wide expression of the CSF-1/CSF-1R pair across breast cancer cell subtypes supports CSF-1/CSF-1R targeting in breast cancer therapy.
authors.affiliation: Dipartimento di Patologia e Oncologia Sperimentali, Università degli Studi di Firenze, and Istituto Toscano Tumori, Firenze, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Morandi
authors.forename: Valentina
authors.initials: V
authors.lastname: Barbetti
authors.forename: Maria
authors.initials: M
authors.lastname: Riverso
authors.forename: Persio
authors.initials: P
authors.lastname: Dello Sbarba
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rovida
mesh_terms: D000818:Animals; D001549:Benzamides; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D015151:Immunoblotting; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D016173:Macrophage Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D016186:Receptor, Macrophage Colony-Stimulating Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
references.citation: Mol Cell Biol. 2002 Jan;22(1):270-85
references.pmid: 11739740
references.citation: J Natl Cancer Inst. 1994 Jan 19;86(2):120-6
references.pmid: 8271294
references.citation: Biochem Biophys Res Commun. 1988 Nov 30;157(1):395-401
references.pmid: 2973787
references.citation: Cancer Res. 1996 Dec 15;56(24):5704-12
references.pmid: 8971179
references.citation: Cancer Res. 2009 Dec 15;69(24):9498-506
references.pmid: 19934330
references.citation: Mol Cancer Ther. 2006 Nov;5(11):2634-43
references.pmid: 17121910
references.citation: Blood. 2002 Jan 1;99(1):111-20
references.pmid: 11756160
references.citation: Leukemia. 2008 Mar;22(3):649-52
references.pmid: 17851554
references.citation: Oncogene. 1991 Jun;6(6):941-52
references.pmid: 1829808
references.citation: Cancer Res. 2008 Jan 1;68(1):18-21
references.pmid: 18172291
references.citation: Blood. 1989 Feb 15;73(3):827-37
references.pmid: 2465043
references.citation: J Exp Med. 2001 Mar 19;193(6):727-40
references.pmid: 11257139
references.citation: J Cell Biochem. 1992 Dec;50(4):350-6
references.pmid: 1334964
references.citation: Bioorg Med Chem Lett. 2008 Jun 15;18(12):3632-7
references.pmid: 18495479
references.citation: Cancer Res. 2006 Apr 15;66(8):4349-56
references.pmid: 16618760
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):173-7
references.pmid: 14734466
references.citation: Nature. 2005 Jul 28;436(7050):518-24
references.pmid: 16049480
references.citation: Oncogene. 1999 Dec 9;18(52):7477-94
references.pmid: 10602507
references.citation: Nat Rev Clin Oncol. 2009 Sep;6(9):535-43
references.pmid: 19652654
references.citation: Cancer Res. 2007 Mar 1;67(5):1918-26
references.pmid: 17332318
references.citation: Blood. 1990 Jan 1;75(1):1-12
references.pmid: 2153029
references.citation: Blood. 2005 Apr 15;105(8):3127-32
references.pmid: 15637141
references.citation: Oncogene. 1989 Aug;4(8):1015-22
references.pmid: 2548144
references.citation: Clin Exp Metastasis. 2008;25(6):629-42
references.pmid: 18461285
references.citation: BMC Cancer. 2006 Apr 18;6:96
references.pmid: 16620391
references.citation: Cancer Res. 2004 Jun 15;64(12):4162-70
references.pmid: 15205327
references.citation: Lab Invest. 2004 Mar;84(3):320-31
references.pmid: 14767486
references.citation: J Clin Invest. 1989 Mar;83(3):921-6
references.pmid: 2646321
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Mol Reprod Dev. 1997 Jan;46(1):71-4
references.pmid: 8981366
references.citation: Exp Biol Med (Maywood). 2004 Jan;229(1):1-11
references.pmid: 14709771
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14404-9
references.pmid: 12381783
references.citation: J Pathol. 2002 Mar;196(3):254-65
references.pmid: 11857487
references.citation: Mol Reprod Dev. 1997 Jan;46(1):11-8
references.pmid: 8981358
references.citation: Nat Rev Cancer. 2006 Mar;6(3):184-92
references.pmid: 16453012
references.citation: Anticancer Res. 2000 Nov-Dec;20(6B):4379-83
references.pmid: 11205275
references.citation: J Leukoc Biol. 1997 Aug;62(2):145-55
references.pmid: 9261328
references.citation: Cell Death Differ. 2006 Nov;13(11):1900-14
references.pmid: 16514418
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1160-7
references.pmid: 19204204
references.citation: PLoS One. 2009 Jul 03;4(7):e6146
references.pmid: 19582160
references.citation: J Leukoc Biol. 1999 Nov;66(5):765-72
references.pmid: 10577508
references.citation: Proc Natl Acad Sci U S A. 1989 Oct;86(20):7924-7
references.pmid: 2554296
references.citation: Breast Cancer Res Treat. 2010 Nov;124(2):567-72
references.pmid: 20563840
references.citation: Methods Enzymol. 1985;116:564-87
references.pmid: 3003518
references.citation: Nat Genet. 2001 Nov;29(3):263-4
references.pmid: 11687795
references.citation: Apoptosis. 2006 Nov;11(11):1909-21
references.pmid: 16927019
references.citation: J Pediatr. 1997 Nov;131(5):748-50
references.pmid: 9403658
references.citation: Cancer Res. 1992 Jul 1;52(13):3661-6
references.pmid: 1535551
references.citation: Bioorg Med Chem. 2010 Mar 1;18(5):1789-97
references.pmid: 20156689
references.citation: Cancer Cell. 2006 Dec;10(6):515-27
references.pmid: 17157791
references.citation: Trends Cell Biol. 2004 Nov;14(11):628-38
references.pmid: 15519852
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Am J Pathol. 2009 Jun;174(6):2347-56
references.pmid: 19443701
references.citation: Adv Cancer Res. 2004;91:1-30
references.pmid: 15327887
references.citation: Cell. 1985 Jul;41(3):665-76
references.pmid: 2408759
references.citation: Clin Cancer Res. 1998 Aug;4(8):1851-6
references.pmid: 9717811
references.citation: Cancer Res. 2002 Sep 15;62(18):5317-24
references.pmid: 12235002
references.citation: Cancer Res. 2004 Aug 1;64(15):5378-84
references.pmid: 15289345
references.citation: N Engl J Med. 2002 Dec 19;347(25):1999-2009
references.pmid: 12490681
references.citation: Cancer Res. 2004 Oct 1;64(19):7022-9
references.pmid: 15466195
references.citation: J Immunol. 2008 Mar 15;180(6):4166-72
references.pmid: 18322228
references.citation: N Engl J Med. 2009 Feb 19;360(8):790-800
references.pmid: 19228622