title: KLF6 inhibits estrogen receptor-mediated cell growth in breast cancer via a c-Src-mediated pathway.
abstract: Estrogen receptors play a key role in breast cancer development and progression. Kruppel-like factor 6 (KLF6) is a tumour-suppressing protein. The aim of this study was to identify the role of KLF6 inhibition in estrogen receptor(alpha) (ERalpha)-elicited breast cancer development. Protein expression levels were examined by western blot analysis and immunoprecipitation was used to analyse interactions between proteins. An MTT assay was used to study cell proliferation. We found that KLF6 mediates cell growth in ERalpha-positive breast cancer cells through interaction with the c-Src protein. This interaction causes inactivation of the Erk and Akt proteins. These pathways are critical for the proliferation and survival of breast cancer cells. We also established that KLF6 could not mediate cell growth in ERalpha-negative cells. We conclude that KLF6 can modulate ERalpha-mediated cell growth in breast cancer cells. The unique role of KLF6 in mediating cell growth in breast cancer cells opens up the possibility of a new therapeutic strategy for treating breast cancer.
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Tian
authors.initials: T
authors.lastname: Du
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yuan
authors.forename: YueMing
authors.initials: Y
authors.lastname: He
authors.forename: Zui
authors.initials: Z
authors.lastname: Tan
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D016392:Proto-Oncogene Proteins pp60(c-src)
references.citation: Eur J Cancer. 2008 Sep;44(13):1895-903
references.pmid: 18691883
references.citation: Cytokine. 2008 Apr;42(1):32-8
references.pmid: 18343154
references.citation: Genomics. 1997 Aug 1;43(3):395-7
references.pmid: 9268646
references.citation: J Gastroenterol Hepatol. 2006 Aug;21(8):1286-9
references.pmid: 16872311
references.citation: J Cell Physiol. 2001 Aug;188(2):143-60
references.pmid: 11424081
references.citation: Hepatology. 2004 Nov;40(5):1047-52
references.pmid: 15486921
references.citation: Ai Zheng. 2002 Oct;21(10):1047-50
references.pmid: 12508640
references.citation: Oncogene. 2004 Oct 28;23(50):8196-205
references.pmid: 15378003
references.citation: Cancer Res. 2004 Jun 1;64(11):3885-91
references.pmid: 15172998
references.citation: J Biol Chem. 1998 Dec 11;273(50):33750-8
references.pmid: 9837963
references.citation: Am J Pathol. 2003 Apr;162(4):1349-54
references.pmid: 12651626
references.citation: Oncogene. 2006 Sep 28;25(44):6026-31
references.pmid: 16702959
references.citation: Science. 2001 Dec 21;294(5551):2563-6
references.pmid: 11752579
references.citation: Cancer Res. 2004 Jun 1;64(11):3838-43
references.pmid: 15172991
references.citation: Int J Cancer. 2003 Jul 10;105(5):625-9
references.pmid: 12740910
references.citation: Int J Cancer. 2007 Sep 15;121(6):1390-5
references.pmid: 17514651
references.citation: APMIS. 2006 Jun;114(6):458-64
references.pmid: 16856969
references.citation: J Pathol. 1996 Dec;180(4):383-8
references.pmid: 9014858
references.citation: Cancer Treat Rev. 2008 Dec;34(8):701-9
references.pmid: 18922644
references.citation: J Cell Physiol. 2008 Mar;214(3):662-72
references.pmid: 17786973
references.citation: Cancer Res. 2008 Feb 15;68(4):965-70
references.pmid: 18250346
references.citation: J Biol Chem. 2006 Jul 28;281(30):20851-20864
references.pmid: 16728403
references.citation: Oncogene. 2005 Jun 30;24(28):4588-90
references.pmid: 15824733
references.citation: J Zhejiang Univ Sci B. 2006 Oct;7(10):830-6
references.pmid: 16972326
references.citation: J Biol Chem. 1997 Apr 4;272(14):9573-80
references.pmid: 9083102
references.citation: Gastroenterology. 2004 Apr;126(4):1090-103
references.pmid: 15057748
references.citation: Clin Cancer Res. 2006 Jun 15;12(12):3730-9
references.pmid: 16778100
references.citation: Semin Cancer Biol. 2001 Oct;11(5):339-52
references.pmid: 11562176