INSULIN-LIKE GROWTH FACTORS AND PROSTATE CARCINOGENESIS

Prostate cancer is the most commonly diagnosed cancer in males. However,
the molecular mechanisms responsible for its development remain unknown.
One of the unique characteristics of prostate adenocarcinoma is that the
clinically recognized cancers represent only a small minority of the ones
present in histological sections at autopsies. Thus, dysregulation of
prostate growth appears to be an extremely common cellular event, while
rapid and metastatic growth is less common and may depend on additional
local or systemic factors. It is as yet unknown what endogenous or
systemic factors regulate this phenomenon. We propose to investigate the
role of the insulin-like growth factors (IGFs), their receptors and
binding proteins (IGFBPs) in the process of prostate carcinogenesis. The
IGFs are important mitogenic factors that have been shown to have
autocrine-paracrine, as well as endocrine roles in normal and malignant
cellular growth. We plan to characterize multiple aspects of the IGF
system in prostate cancer, to identify and analyze specific alterations
in the circulating IGFs and IGFBPs in the sera of humans with prostate
cancer and in an animal model of prostate cancer, and to investigate the
possibility that the proteolytic action of prostate specific antigen on
IGFBPs is a growth stimulant in prostate cancer. Our resources include
an established 3 year collaboration between scientists with expertise in
the molecular biology and biochemistry of the insulin-like growth
factors, the cell biology of cultured prostatic cells, the biochemistry
of prostate specific antigen and in clinical urology, which have already
produced a number of contributions to our understanding of prostate
cancer. We believe that a thorough analysis of the role of the IGFs in
prostatic cell growth will result in important insights into the
fundamental regulation of prostatic carcinogenesis, and provide
potentially valuable diagnostic and therapeutic findings.