Mouse Model to Screen for Distal PI3 Kinase Inhibition in the Prostate
Washington University in St. Louis
posted on 03/07/2007
The current invention describes a prostate specific mTOR knockout mouse generated by crossing TSC1-LoxP mice with transgenic mice expressing cre recombinase under the control of the androgen promoter. Without TSC1 expression, these mice constitutively express mTOR and S6K in the prostate, and display a marked increase in phosphorylated S6K protein in prostate epithelial cells.
Suggested Uses
- Screening for novel prostate cancer therapeutics associated with inhibiting the PI3K pathway.
- Evaluation of potential mTOR or S6K inhibitors.
- Research involving the PI3K pathway and its downstream targets, mTOR and S6K.
Advantages
Advantages of this TSC1 knockout mouse include easy detection of S6K protein using a two-step immunohistochemistry approach that labels S6K positive cells a bright green color and the ease of quantification of S6K positive cells due to the anatomy of the prostate.
Detailed Description
Background:
The mammalian target of rapamycin (mTOR) regulates cell growth and proliferation as a downstream target of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (Akt). mTOR is a key regulator of protein translation that, when activated, allows mRNA recruitment to the ribosome and phosphorylates the 70 kD ribosomal protein, S6K, to further enhance ribosome efficiency. In this pathway, the tumor suppressors tuberous sclerosis complex 1 (TSC1) and TSC2 negatively regulate mTOR activity to inhibit protein translation.
Technology Description:
The current invention describes a prostate specific mTOR knockout mouse generated by crossing TSC1-LoxP mice with transgenic mice expressing cre recombinase under the control of the androgen promoter. Without TSC1 expression, these mice constitutively express mTOR and S6K in the prostate, and display a marked increase in phosphorylated S6K protein in prostate epithelial cells. Advantages of this TSC1 knockout mouse include easy detection of S6K protein using a two-step immunohistochemistry approach that labels S6K positive cells a bright green color and the ease of quantification of S6K positive cells due to the anatomy of the prostate.
File Number: CU0688
This innovation currently is not available for online licensing. Please contact Erin Brosnahan at Washington University in St. Louis for more information.
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