title: miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation.
abstract: BACKGROUND
  Pertuzumab is a humanized mAb that binds to the extracellular region of HER2/ErbB2 and is approved for treating breast cancer. Although ovarian cancer and breast cancer have comparable levels of HER2/ErbB2 expression, clinical studies of pertuzumab in epithelial ovarian cancer patients have not met the same level of success.
  
  
  OBJECTIVE
  To investigate the molecular mechanisms by which pertuzumab exerts its anti-tumor effects in ovarian cancer and the mechanisms by which cancer cells achieve pertuzumab resistance.
  
  
  METHODS
  We examined expression of miR-150 in ovarian cancer cells treated with pertuzumab or not. miR-150 knockdown impacts on pertuzumab treatment were analyzed by cell proliferation assay, apoptosis analysis and cell cycle analysis. Cell signal pathway was examined by western blot assay.
  
  
  RESULTS
  Pertuzumab induced miRNA-150 expression in SKOV3 and SNU119 cells. Furthermore, suppression of miRNA-150 in both cell lines resulted in decreased drug sensitivity to pertuzumab and cell apoptosis. The blockage of G1/S checkpoint by pertuzumab was rescued as well. miRNA-150 knockdown activated PI3K-Akt pathway and LY294002 reversed the effect of miR-150 knockdown.
  
  
  CONCLUSIONS
  miRNA-150 downregulation may contribute to the pertuzumab resistance in ovarian cancer via, at least in part, PI3K-akt pathway.
authors.affiliation: Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
authors.forename: Delinaer
authors.initials: D
authors.lastname: Wuerkenbieke
authors.affiliation: Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China. cailingma117@126.com.
authors.forename: Cailing
authors.initials: C
authors.lastname: Ma
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D000077216:Carcinoma, Ovarian Epithelial; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009025:Morpholines; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D002867:Chromones; D035683:MicroRNAs; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: Drug resistance; Ovarian cancer; Pertuzumab; miR-150