PMID- 25187457
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20220327
IS  - 1008-9292 (Print)
IS  - 1008-9292 (Linking)
VI  - 43
IP  - 4
DP  - 2014 Jul
TI  - [Generation and comparison of two genetically engineered mouse models of 
      ErbB2/Neu positive-PTEN deficient breast cancer].
PG  - 427-33
AB  - OBJECTIVE: To generate two genetically engineered mouse models of ErbB2/Neu 
      positive-PTEN deficient breast cancer and to compare their biological properties. 
      METHODS: 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. RESULTS: 
      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. CONCLUSION: 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.
FAU - Wang, Qing-fei
AU  - Wang QF
AD  - Department of Clinical Laboratory, Nanjing Drum Tower Hospital, School of 
      Medicine, Nanjing University, Nanjing 210008, China.
FAU - Ding, Hui
AU  - Ding H
AD  - Department of Clinical Oncology, Nanjing Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing 210008, China.
FAU - Liu, Bao-rui
AU  - Liu BR
AD  - Department of Clinical Oncology, Nanjing Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing 210008, China.
FAU - Zhang, Kui
AU  - Zhang K
AD  - Department of Clinical Laboratory, Nanjing Drum Tower Hospital, School of 
      Medicine, Nanjing University, Nanjing 210008, China.
LA  - chi
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhejiang Da Xue Xue Bao Yi Xue Ban
JT  - Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical 
      sciences
JID - 100927946
RN  - EC 2.7.10.1 (Erbb2 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*genetics
MH  - *Disease Models, Animal
MH  - Female
MH  - Gene Deletion
MH  - *Mammary Neoplasms, Animal
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - PTEN Phosphohydrolase/*genetics
MH  - Receptor, ErbB-2/*genetics
EDAT- 2014/09/05 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/09/05 06:00
PHST- 2014/09/05 06:00 [entrez]
PHST- 2014/09/05 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.3785/j.issn.1008-9292.2014.07.005 [doi]
PST - ppublish
SO  - Zhejiang Da Xue Xue Bao Yi Xue Ban. 2014 Jul;43(4):427-33. doi: 
      10.3785/j.issn.1008-9292.2014.07.005.