title: Transforming growth factor-β1 regulation of ATF-3, c-Jun and JunB proteins for activation of matrix metalloproteinase-13 gene in human breast cancer cells.
abstract: Transforming growth factor-beta1 (TGF-β1) plays a significant role in breast cancer mediated bone metastasis, and it stimulated expression of matrix metalloproteinase-13 (MMP-13; an invasive and metastasis gene) via activating transcription factor-3 (ATF-3) in human breast cancer cells (MDA-MB231). We further dissected the role of ATF-3 and its interacting proteins (activator protein-1; AP-1) for TGF-β1-stimulation of MMP-13 expression in these cells. Chromatin immunoprecipitation (ChIP) experiment identified the TGF-β1-stimulation of ATF-3 interaction at the AP-1 site of the MMP-13 promoter in a sustained and prolonged manner in MDA-MB231 cells. In silico protein-protein interaction, co-immunoprecipitation and western blot experiments identified the ATF-3 interaction and regulation of c-Jun and JunB proteins in these cells. The sequential ChIP assay confirmed the presence of c-Jun/ATF-3 complex at the AP-1 site of the MMP-13 promoter in MDA-MB231 cells upon TGF-β1-treatment. Hence, our results suggested that TGF-β1-treatment stimulated a sustained and prolonged expression of ATF-3, and its interaction and regulation of c-Jun protein and their assembly as a protein complex at the AP-1 site of the MMP-13 promoter could be responsible for MMP-13 gene activation in MDA-MB231 cells.
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: M
authors.initials: M
authors.lastname: Gokulnath
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Swetha
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: G
authors.initials: G
authors.lastname: Thejaswini
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.
authors.forename: P
authors.initials: P
authors.lastname: Shilpa
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India. Electronic address: selvamurugan.n@ktr.srmuniv.ac.in.
authors.forename: N
authors.initials: N
authors.lastname: Selvamurugan
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D001483:Base Sequence; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; C581727:JunB protein, human; C508960:TGFB1 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: ATF-3; Breast cancer; JunB; MMP-13; TGF-β1; c-Jun