title: Akt and phospholipase Cγ are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin.
abstract: BACKGROUND
  Epidemiological studies revealed a strong correlation between the metabolic syndrome/diabetes mellitus type 2 (DM2) and higher incidence and faster progression of breast and colon cancer. However, the underlying molecular mechanisms are widely unknown. Akt and phospholipase Cγ (PLCγ) are involved in tyrosine kinase signaling and promote tumor cell growth and migration. Therefore, we examined regulatory functions and expression of Akt and PLCγ in a simplified in vitro diabetogenic model.
  
  
  RESULTS
  Protein expression was determined by western blot analysis in MDA-MB-468 breast cancer and SW480 colon cancer cells previously cultured under physiologic (5.5 mM) and diabetogenic (11 mM) glucose concentrations (without and with 100 ng/ml insulin). We studied the culture effects on proliferation and migration of these cells, especially after inhibiting Akt and PLCγ. We found that Akt expression was up-regulated with high glucose and insulin in both cell lines, whereas PLCγ expression was enhanced in colon cancer cells only. High levels of glucose and insulin increased cell proliferation and migration in both cell lines in vitro, mediated by Akt and PLCγ, as shown through the specific pharmacological inhibitors A6730 and U73122.
  
  
  CONCLUSIONS
  Our molecular data explain glucose- and insulin-induced changes in a cancer cell and help to understand what might trigger tumor cell proliferation and migration in DM2 patients, too.
authors.affiliation: Institute of Immunology and Experimental Oncology, Witten/Herdecke University, Stockumer Str, 10, D-58448, Witten, Germany. nicola.tomas@uni-wh.de
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Tomas
authors.forename: Kai
authors.initials: K
authors.lastname: Masur
authors.forename: Jonas C
authors.initials: JC
authors.lastname: Piecha
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zänker
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D004963:Estrenes; D007004:Hypoglycemic Agents; D007328:Insulin; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma; D005947:Glucose