title: Cyclooxygenase-2 and Akt mediate multiple growth-factor-induced epithelial-mesenchymal transition in human hepatocellular carcinoma.
abstract: OBJECTIVE
  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma (HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies.
  
  
  METHODS
  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined.
  
  
  RESULTS
  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin E2 (PGE2), Akt and phosphorylated Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT.
  
  
  CONCLUSIONS
  Multiple growth factors induce EMT in HCC. COX-2 and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Olorunseun O
authors.initials: OO
authors.lastname: Ogunwobi
authors.forename: Ton
authors.initials: T
authors.lastname: Wang
authors.forename: Lucy
authors.initials: L
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
mesh_terms: D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D017690:Cell Transplantation; D024042:Collagen Type I / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D015820:Cadherins; D024042:Collagen Type I; D005353:Fibronectins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D000515:alpha 1-Antitrypsin; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; D051058:Oncogene Protein v-akt; D015232:Dinoprostone
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