title: [Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer].
abstract: To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties.
  
  
  
  The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed.
  
  
  
  Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models.
  
  
  
  Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.
authors.affiliation: Department of Clinical Laboratory, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Qing-fei
authors.initials: QF
authors.lastname: Wang
authors.affiliation: Department of Clinical Oncology, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Clinical Oncology, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Bao-rui
authors.initials: BR
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D015674:Mammary Neoplasms, Animal; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse; C487757:Pten protein, mouse