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Model Characteristics - Model:
NRL-PRL MMTV-Cre Jak2fl/fl
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| Model Descriptor |
NRL-PRL MMTV-Cre Jak2fl/fl
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| Official Nomenclature |
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| Genotype |
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| Species |
Mouse (Mus musculus)
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| Strain |
mixed
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| Is This a Tool Strain? |
No
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Developmental Stage
(applies only to Zebrafish) |
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| Experimental Design |
The prolactin receptor (PRLR), its associated Janus kinase 2 (Jak2) and the signal transducer and activator of tranion 5 (Stat5) are essential for normal mammary gland development. Owing to the upregulation of the PRLR and the local synthesis of its ligand in neoplastic cells, it has been proposed that PRL can act as a local growth factor in human breast cancers. This notion is supported by experimental evidence in transgenic mice, which showed that the mammary-specific expression of PRL contributes to carcinogenesis in vivo. To assess the importance of Jak2/Stat5 signaling during mammary cancer initiation and progression, we generated a mouse model in a predominantly FvB background (50-75%) that overexpresses PRL in the mammary epithelium that is conditionally deficient in Jak2. Using Cre-mediated recombination, we deleted the Jak2 gene before or after neoplastic transformation. This unique approach allowed us to discriminate the role of the Jak2/Stat5 pathway during the initiation of mammary neoplasia, as well as the growth and survival of fully neoplastic mammary cancer cells in vitro and in vivo.
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| Phenotype |
Collectively, the results of this study show that the functional ablation of Jak2 protects against the onset of PRL-induced mammary tumorigenesis, suggesting that targeting this kinase is a relevant strategy for mammary cancer prevention. Surprisingly, Jak2 deficiency did not affect the growth and survival of PRL-induced mammary cancer cells in culture and in vivo. Consequently, Jak2 cannot be a sole therapeutic target to treat the established disease. PRL-induced mammary cancers exhibited an upregulation of ErbB2 and other ErbB receptor tyrosine kinases that may supersede the functionality of PRLR signaling through Jak2.
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| Website for add. info |
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| Breeding Notes |
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| Sex Distribution of the Phenotype |
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| Submitted by |
caMOD, Curator
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| Principal Investigator / Lab |
Wagner, Kay-Uwe
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| Comment |
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| Model Availability: This model is available from |
| Strain |
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