Abstract
Transgenic mice expressing the Notch 4 intracellular domain (ICD) (Int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. Notch4 signaling is mediated primarily through the interaction of Int3 with the transcription repressor/activator Rbpj. We have conditionally ablated the Rbpj gene in the mammary glands of mice expressing whey acidic protein (Wap)-Int3. Interestingly, Rbpj knockout mice (Wap-Cre+/Rbpj-/-/Wap-Int3) have normal mammary gland development, suggesting that the effect of endogenous Notch signaling on mammary gland development is complete by day 15 of pregnancy. RBP-J heterozygous (Wap-Cre+/Rbpj-/+/Wap-Int3) and Rbpj control (Rbpj flox/flox/Wap-Int3) mice are phenotypically the same as Wap-Int3 mice with respect to mammary gland development and tumorigenesis. In addition, the Wap-Cre+/Rbpj-/-/Wap-Int3-knockout mice also developed mammary tumors at a frequency similar to Rbpj heterozygous and Wap-Int3 control mice but with a slightly longer latency. Thus, the effect on mammary gland development is dependent on the interaction of the Notch ICD with the transcription repressor/activator Rbpj, and Notch-induced mammary tumor development is independent of this interaction.
Original language | English (US) |
---|---|
Pages (from-to) | 219-230 |
Number of pages | 12 |
Journal | Oncogene |
Volume | 28 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2009 |
Keywords
- Int3
- RBP-J
- Tumorigenesis
ASJC Scopus subject areas
- Genetics
- Molecular Biology
- Cancer Research