Although prostatic adenocarcinoma is the most commonly diagnosed cancer in U.S. males, the death rate from this cancer is lower than would be expected. African Americans (AAs) who have prostate cancer (PCa) typically have more aggressive disease and make up a disproportionate number of the deaths from this disease; however, many patients with PCa will not die of PCa even if untreated (i.e., indolent prostate cancer). We have recently studied the expression of the molecule, Kaiso, in PCa and found that Kaiso is increased in aggressive PCa, especially in PCa in AAs. Also, we have found that Kaiso is involved in facilitating the epigenetic suppression of genes (e.g., E-cadherin), and via this silencing of specific genes, causing epithelial to mesenchymal transition (EMT) and androgen resistance of PCa. The objectives of our proposal are to demonstrate that the nuclear expression of Kaiso is mediated through EGFR signaling and that Kaiso can be targeted therapeutically to reduce EMT and associated metastases of PCa. To accomplish this, we have outlined three specific aims.

Public Health Relevance

This collaborative Full Project between Tuskegee University and the UAB CCC focuses on determining the role of genetic regulators (Kaiso-mediated) contributing to prostate cancer metastasis. The findings from this study will provide preclinical evidence for the development of Kaiso-specific inhibitors as therapeutic options for prostate cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA118948-12
Application #
9357538
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2005-09-30
Project End
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
12
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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