GROWTH AND DEATH SIGNALS IN THE PROSTATE

Project: Research project

Project Details

Description

The scientific goal of this proposal is to understand the subcellular
signaling pathways involved in growth and timely death of prostate
epithelial cells. Androgen deprivation leads to apoptosis of normal
and prostate cancer cells. Several lines of evidence support the
hypothesis that receptor tyrosine kinase signaling pathways in
combination with anti-apoptosis protein protect the prostate cell
from death. Our preliminary data androgen-independent growth. We
hypothesize that aberrant signaling by receptor tyrosine kinases such
as HER-2/neu leads to downstream activation of the mitogen-activated
protein kinase (MAPK) pathway and enhanced anti-apoptotic function of
bcl-2 family members. The first and second specific aims will
explore two branches of the MAPK pathway downstream of HER-2/neu,
Raf-1 and MEKK1, and their role in androgen-independent prostate cell
growth. The final aim of this proposal will translate the in vitro
work to an in vivo mouse model of prostate development using
prostate-specific expression of a HER-2/neu transgene.

As a gastroenterologist and scientist, I am interested in studying
immune-epithelial interactions in the intestinal mucosa. My research
has begun to address the molecular mechanisms involved in intestinal
epithelial cell apoptosis in response to lymphocyte-mediated stimuli.
I realize, however, that in order to answer the next tier of research
questions as an independent investigator, I require additional
training. The training most appropriate to complement my previous
research experience and to facilitate the transition to independence
is in the area of signal transduction. The laboratory of the sponsor
uses advanced molecular biologic methods to manipulate signal
transduction pathways in epithelial systems. The research proposal
outlined in this grant has been carefully chosen for both its
scientific merit and the skills required to answer the questions.
Although the model system described is the prostate, the approach
required to study regulation of apoptosis and growth factor-dependent
growth can be applied to other epithelia. In addition to the hands-
on laboratory work, I will be taking graduate-level courses in
cellular and molecular biology. After this three year period of
training, I will return to gastrointestinal research with the support
of my co-sponsor and begin to develop intestinal models to study
normal and pathologic states of apoptosis.
StatusFinished
Effective start/end date6/15/983/31/03

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $124,605.00
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases: $119,205.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $119,205.00
  • National Institute of Diabetes and Digestive and Kidney Diseases

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