title: TIMP4 Modulates ER-α Signalling in MCF7 Breast Cancer Cells.
abstract: Tissue inhibitor of metalloprotease 4 (TIMP4) contributes to poor prognosis in breast and other tumours. However, the mechanisms of how TIMP4 influences breast cancer cell behaviour are unknown. Our aim was to explore the signalling pathways modulated by TIMP4 in breast cancer cells. Human recombinant TIMP4 was added to MCF7 breast cancer cells and RNASeq was performed. TIMP4 RNASeq results were validated by RT-PCR. Network analyses of TIMP4-exposed cells showed that ER-α, HIF1A and TGF-β signalling were activated, whereas FOXO3 signalling was downregulated. ER-α protein levels were increased and concordantly, promoters of TIMP4-upregulated genes were significantly enriched in oestrogen-binding sites. We concluded that TIMP4 modulates multiple signalling pathways relevant in cancer in MCF7 cells, including the ER-α cascade.
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Pruefer
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: K
authors.initials: K
authors.lastname: Vazquez-Santillan
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Munoz-Galindo
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: J L
authors.initials: JL
authors.lastname: Cruz-Colin
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Maldonado
authors.affiliation: Functional Genomics Laboratory and Epigenetics Laboratory, Basic Research Subdirection. Instituto Nacional de Medicina Genómica. México City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Melendez-Zajgla
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000503:physiopathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D047628:Estrogen Receptor alpha; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C506487:ESR1 protein, human