title: In vitro assessment of the effects of anti-HER2 monoclonal antibodies on proliferation of HER2-overexpressing breast cancer cells.
abstract: BACKGROUND
  HER2 proto-oncogene is critical in the biology of breast cancer and an important therapeutic target of monoclonal antibodies (mAbs). We have recently established a panel of anti-HER2 mAbs recognizing different epitopes within the extracellular domain of HER2.
  
  
  METHODS
  In the present study the antiproliferative effect of these mAbs was investigated on HER2-overexpressing human breast cancer cell line BT474, using radioactive thymidine incorporation assay.
  
  
  RESULTS
  Our results demonstrated that while two of the mAbs (1T0 and 2A8) inhibited cell proliferation dose dependently, similar to trastuzumab, six mAbs (1F2, 1B5, 1H9, 4C7, 1H6 and 2A9) augmented cell proliferation. Treatment of BT474 cells with different combinations of two mAbs induced either synergistic inhibitory or stimulatory effects.
  
  
  CONCLUSIONS
  Our findings indicate that combination of some stimulatory mAbs could completely abolish the inhibitory effect of other mAbs against HER2. Employment of some combinations of mAbs with significant synergistic inhibitory function may improve the therapeutic efficacy of HER2-specific mAbs.
authors.affiliation: Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Fathollah
authors.initials: F
authors.lastname: Tahmasebi
authors.forename: Tohid
authors.initials: T
authors.lastname: Kazemi
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Amiri
authors.forename: Jalal
authors.initials: J
authors.lastname: Khoshnoodi
authors.forename: Jafar
authors.initials: J
authors.lastname: Mahmoudian
authors.forename: Ali Ahmad
authors.initials: AA
authors.lastname: Bayat
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.forename: Hodjatallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000939:Epitopes; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human