MOLECULAR/CELLULAR PATHWAYS OF BLADDER CA++ PROGRESSION

Project: Research project

Project Details

Description

The Bladder Cancer Program at the University of Southern
California/Kenneth Norris Comprehensive Cancer Center is an integrated and
multidisciplinary program that has made important contributions in
clinical investigations as well as basic and translational research in
bladder cancer. Our group has identified important genetic alterations
associated with bladder cancer tumorigenesis and progression, including 9q
and 17p allelic loss and p53 mutations. More recently, we have identified
homozygous deletions and point mutations in p16 (CDKN2) in squamous
carcinomas of the bladder, and have found that DNA methylation of exon 1
is associated with loss of expression of the p16 tumor suppressor gene.
These studies have led to the development of an evolving model of bladder
tumorigenesis and progress. Based on the depth of our clinical and basic
science programs, we have developed a strong translational research
program; we have recently defined the clinical significance of p53 protein
alterations in bladder cancer. While we and others have shown that p53
and Rb are central in bladder cancer progression, the mechanisms by which
this occurs are not well understood. The studies proposed here will
examine several interrelated molecular and cellular pathways involved in
bladder tumor progression, including: (1) the significance of
angiogenesis in bladder cancer, including study of the mechanisms of
angiogenesis regulation by p53; (2) the relationship of p53 and Rb
alterations to bladder cancer progression, mechanisms of loss of tumor
suppressor function that do not involve gene mutations or deletions, and
the effects of tumor suppressor inactivation; (3) the role of DNA
methylation in tumor suppressor gene silencing and as a possible marker
for bladder cancer diagnosis and screening; (4) the detection and clinical
significance of occult lymph node and bone marrow micrometastases in
patients with bladder cancer, and mechanisms by which early tumor
dissemination occurs.

We further propose that the study of angiogenesis and the detection of
occult micrometastases in patients with bladder cancer will be excellent
candidates for Bladder Cancer Network collaborative studies. Based on our
past work, the progress of our current studies, and our strong ongoing
patient and tissue resources, our group is in an excellent position to
continue to make important contributions to the study of bladder cancer,
and to become valuable collaborators in the Bladder Cancer Network.
StatusFinished
Effective start/end date4/19/963/31/01

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

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