Generation and comparison of two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer / 浙江大学学报·医学版
Journal of Zhejiang University. Medical sciences
;
(6): 427-433, 2014.
Article
in Chinese
| WPRIM
| ID: wpr-251685
ABSTRACT
<p><b>OBJECTIVE</b>To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Breast Neoplasms
/
Mice, Transgenic
/
Mammary Neoplasms, Animal
/
Gene Deletion
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Mammary Tumor Virus, Mouse
/
Receptor, ErbB-2
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Disease Models, Animal
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PTEN Phosphohydrolase
/
Genetics
Limits:
Animals
Language:
Chinese
Journal:
Journal of Zhejiang University. Medical sciences
Year:
2014
Type:
Article
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