BPH GROWTH REGULATION MODEL

Project: Research project

Project Details

Description

The broad, long-term objective of this proposal is to elucidate the
mechanism of the growth regulation of basic fibroblast growth factor
(bFGF) and its related growth factor int-2 in the development of benign
prostatic hyperplasia (BPH). The research proposed here is dedicated to
the employment of int-2 transgenic mice as a benign prostate hyperplasia
model system to investigate the role of int-2 growth factor in the
ontogenesis of BPH in a prostate specific manner. The basic assumption
of this proposal is that the development of BPH is due to the deregulated
growth factor expression and the pathogenesis of BPH can be reproduced by
manipulating the interactions between the cells that exhibit aberrant
growth factor production and their surrounding tissues. one major goal of
this proposal is to elucidate the molecular mechanism of int-2 induced
prostatic hyperplasia and apply this observation to further our
understanding of possible mechanisms for bFGF in BPH development. To
achieve this goal, we will pursue the following specific aims: (1)
Examine the molecular and histopathological effect of int-2 growth factor
overexpression on prostatic growth regulation and BPH development. (2)
Analyze the mesenchymal-epithelial interaction of BPH development
employing transgenic mice tissue recombination. (3) Examine int-2 growth
factor overexpression modulated ECM expression in vitro using cells
derived from int-2 transgenic mouse prostate. (4) Establish a basic
fibroblast growth factor (bFGF) transgenic founder line that employs a
bigenic system for prostate specific expression. A recently developed
binary system for regulating transgene expression in transgenic mice
generation will be employed in the construction of bFGF transgenic mice.
The basic experimental design involves the manipulation of hyperplastic
prostate growth by interfering with the int-2 growth factor activity so
that a measurable phenotypic change can be studied. Analyses of the
results obtained from the research proposed here will help us gain more
insights into how growth factors from bFGF family modulate the
mesenchymal-epithelial interactions as well as their role in the growth
control and development of BPH.
StatusFinished
Effective start/end date9/30/929/29/98

Funding

  • National Institutes of Health: $186,581.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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