title: Tissue inhibitor of metalloproteinases-2 growth-stimulatory activity is mediated by nuclear factor-kappa B in A549 lung epithelial cells.
abstract: Tissue inhibitors of metalloproteinases (TIMPs) are pleiotropic factors that function as key regulators of extracellular matrix remodeling. They exhibit multifunctional roles including cell growth-stimulating activities and protection from apoptosis. In the present study, we showed that human recombinant TIMP-2 (hrTIMP-2) promotes growth of A549 lung cells. This effect was accompanied by increase in nuclear factor-kappa B (NF-kappaB) activity 24h after exposure as determined by electrophoretic mobility shift assay (EMSA) analysis. This effect was correlated with downregulation of IkappaBalpha and beta proteins and later increases in Bcl-3, IkappaB, and cyclin D1 proteins. Blocking induction of NF-kappaB activity using a dominant-negative mutated version of IkappaBalpha abrogated NF-kappaB activation and cell proliferation.
authors.affiliation: Laboratorio de Biologia Molecular Subdirección de Investigación Básica, Instituto Nacional de Cancerología (INCan), Av. San Fernando 22, Tlalpan, 14080 México City, DF, Mexico.
authors.forename: Floria
authors.initials: F
authors.lastname: Lizárraga
authors.forename: Vilma
authors.initials: V
authors.lastname: Maldonado
authors.forename: Jorge
authors.initials: J
authors.lastname: Meléndez-Zajgla
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D008168:Lung / Q000166:cytology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D019716:Tissue Inhibitor of Metalloproteinase-2; D019938:Cyclin D1; D000072000:NF-KappaB Inhibitor alpha; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human