Aging and Prostatic Hyperplasia in Transgenic Mice

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Age-associated benign prostatic
hyperplasia (BPH) is a major health problem of elderly men. The molecular
etiology of BPH is complex and not clearly understood. Chronic influence of
multiple regulatory factors including androgen and peptide growth factors are
suspected to contribute to pro static cell proliferation and pathogenesis. The
species-specific nature of BPH and the lack of an appropriate mouse model have
impeded progress in the delineation of the causal factors for the development
of BPH and testing of potential intervention strategies. It is our hypothesis
that prostate-specific overexpression of the androgen receptor (AR) and
insulinlike growth factor-1 (IGF- 1) in transgenic mice would cause increased
prostatic cell proliferation and would give rise to a pathological condition
similar to human BPH. The first specific aim of this proposal is to generate
transgenic mice overexpressing AR in the prostate targeted by a ten kilobase
pair long homologous mouse probasin gene promoter and to characterize the age-and
androgen-dependent changes in the prostatic morphology, cellular
composition and gene expression profiles. Region (proximal, intermediate and
distal)- and lobe-specific histopathologic changes during aging will be
correlated with gene expression profiles determined by micro array analysis. In
the second specific aim, we will elucidate the interacting role of AR and IGF-1
in promoting aberrant cell proliferation and gene expression through
comparative analysis of monotransgenic mice with individual prostatic
overexpression of AR and IGF- 1 and bitransgenic mice with simultaneous
overexpression of both AR and IGF- 1 in the prostate. Our preliminary results
support the feasibility of the proposed experiments and successful completion
of this study is expected to provide important new insights into the cellular
and molecular pathways that lead to the development of the prostatic
hyperplasia under the influence of physiological stimuli. Additionally, the
transgemc model and molecular markers generated through these investigations
will be beneficial for future studies concerning the development of effective
intervention strategies and progression/remission of the disease process.
StatusFinished
Effective start/end date9/1/028/31/07

Funding

  • National Institutes of Health: $252,856.00
  • National Institutes of Health: $253,711.00
  • National Institutes of Health: $252,856.00

ASJC

  • Medicine(all)

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