The developing prostate has the highest rate of cell proliferation which subsequently ceases in the mature adult, resulting in a growth quiescent gland. We have focused on the morphogenesis of the mouse dorsal prostatic lobes and have identified proteins by mass spectrometry in the developing 4 week prostate that are absent in the mature 10 week prostate. These proteins will be characterized further and those which meet the criteria that they are: 1) expressed during normal prostate development in the 4 week old prostate, 2) absent in the 10 week growth quiescent prostate, 3) regulated by androgens, 4) continue to be expressed in the LPB-Tag model for prostate cancer and 5) epithelial cell specific will be utilized to develop novel models for prostate cancer. We have the composite probasin promoter (ARR2PB) which is prostate epithelial cell specific and which targets high levels of transgene expression to the mouse prostate. The transgenic mouse models will allow us to analyze the effects of over-expressing these endogenous proteins on the growth and differentiation of the normal prostate gland and to determine their role in the development of prostate cancer. Our HYPOTHESIS is that proteins that regulate normal prostate morphogenesis may promote the development of prostate cancer.
The Specific Aims of this proposal are:
Specific Aim I. To characterize the proteins previously identified in the growing 4 week prostate which are absent in the 10 week growth quiescent prostate.
Specific Aim II. To define the expression of these proteins in the developing prostate and determine whether they are re-expressed in prostate cancer (using the LPB-Tag model for prostate cancer).
Specific Aim III. To determine the function of these proteins in prostate tumorigenesis using the transgenic mouse model.
