title: PI3K is required for both basal and LPA-induced DNA synthesis in oral carcinoma cells.
abstract: BACKGROUND
  The glycerophospholipid lysophosphatidic acid (LPA), which is present in most tissues and in high concentrations in saliva, may exert profound effects on oral cancer cells. We have investigated mitogenic signalling induced by LPA in the two oral carcinoma cell lines, D2 and E10, focusing on the role of EGFR transactivation and downstream pathways.
  
  
  METHODS
  Two oral squamous carcinoma cell lines, D2 and E10, were analysed for effects of LPA on signalling pathways and induction of DNA synthesis. Pathway activation was investigated by examining phosphorylation of signalling proteins and by the use of specific pathway inhibitors.
  
  
  RESULTS
  The D2 cells had higher levels of activated signalling proteins and higher DNA synthesis activity in the basal condition than E10 cells. EGF did not induce proliferation in D2 cells, whereas LPA induced proliferation in both cell lines, by mechanisms depending on EGFR transactivation. Release of EGFR ligands was involved in basal and LPA-induced proliferation in both D2 and E10 cells. The proliferation in D2 cells was dependent on the PI3K/Akt pathway, but not the MEK/ERK pathway. In E10 cells, the PI3K/Akt, MEK/ERK and p38 pathways were all involved in the proliferation.
  
  
  CONCLUSIONS
  Transactivation of EGFR is required for LPA-induced DNA synthesis in D2 and E10 cells. Our results also show that although proliferation of oral carcinoma cells is regulated by several pathways, and differentially in E10 and D2 cells, the PI3K pathway has a crucial role in both cell lines.
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aasrum
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.|Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Vegard
authors.initials: V
authors.lastname: Tjomsland
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.|Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: G Hege
authors.initials: GH
authors.lastname: Thoresen
authors.affiliation: Clinic for Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Paula M
authors.initials: PM
authors.lastname: De Angelis
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Christoffersen
authors.affiliation: Department of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.|Department of Oral Biology and Department of Paediatric Dentistry and Behavioural Science, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Ingvild J
authors.initials: IJ
authors.lastname: Brusevold
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D000077195:Squamous Cell Carcinoma of Head and Neck; D015533:Transcriptional Activation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; C032881:lysophosphatidic acid
keywords: EGFR; LPA; oral squamous carcinoma