Accession Number:

ADA394726

Title:

Determining Gene Expression, Substrate Specifically and Natural Substrates for Prostate Associated Proteases

Descriptive Note:

Annual rept. 1 Jul 2000-30 Jun 2001

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

2001-07-01

Pagination or Media Count:

26.0

Abstract:

Numerous studies have shown that proteolytic enzymes play an essential role in tumor invasion, metastasis and angiogenesis 1,2, 3. Proteases may enhance these processes through the release andor activation of growth factors and the degradation of extracellular matrix. Thus, inhibition of these protease-mediated processes may be a therapeutic strategy for the treatment of metastatic cancer. Indeed, proteases, in general, have proven to be excellent chemotherapeutic targets as evidenced by the HIV protease inhibitors and the large number of successful clinical trials involving protease inhibitors 4. This proposal focused upon serine proteases of the chymotrypsin fold due to the wealth of information that exists on structure-function relationships regarding this class of enzymes and the existence of potent and specific inhibitors that are readily available for their inhibition. In addition, understanding of the function of these proteases may lead to further insight into cancer biology and may lead to possible therapeutics. In particular, we proposed to understand serine protease function by identifying serine protease substrates and substrate specificity. These techniques used and developed should become increasingly useful as the Human Genome Project continues to provide numerous serine protease genes whose products have no known function. These studies should be generalizable to other classes of proteases and to other enzymes such as kinases. In addition, perhaps a greater understanding of prostate and prostate cancer biology can be gained by examining the interaction of the proteases and downstream substrates within a tumor tissue and during various stages of cancer.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE