Abstract

Prostate cancer is the most common cancer and the second leading cause of cancer death in American men. The American Cancer Society estimates approximately 180,400 new cases of prostate cancer will be diagnosed and 31,900 men will die of this disease during 2000 in this country. Early detection is probably one of the most important and effective strategies for combating this major disease. PSA is the most useful marker for detection of prostate cancer. However, the specificity is still not sufficient, even though the PSA test has recently been greatly improved. About 75 percent of the men who undergo prostate needle biopsies for mildly elevated PSA values do not have prostate carcinoma.
The aim of this project is to continue the efforts to develop and improve new tests for the detection of prostate cancer. Highly specific and sensitive immunoassays for serum human kallikrein 2 (hK2) have been developed for prostate cancer detection. The applicant showed the levels of hK2, a prostate-specific secretary protein, are not well correlated with the levels of PSA in prostate cancer patients, indicating that hK2 is potentially a useful marker. Furthermore, preliminary studies suggest that hK2 may also aid in cancer detection because the applicant showed that the percentfree PSA (FPSA) and total hK2/FPSA can increase the specificity of cancer detection when PSA is 2-4 ng/ml. The applicant proposes to perform a prospective study to demonstrate the usefulness of an hK2 test for prostate cancer detection. He will also study whether an hK2 test will be useful for monitoring and managing prostate cancer patients treated by chemotherapies or prostatectomies. Moreover, the applicant has cloned a PSA splicing varient (PSA-v), which supposedly produces a secreted variant of the PSA protein with a different C -terminal sequence from the wild type PSA. He will develop highly sensitive and specific immunoassays for PSA-v in order to enhance the performance of current PSA tests and to reduce the number of unnecessary biopsies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070892-07
Application #
6513007
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Kagan, Jacob
Project Start
1996-05-01
Project End
2006-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
7
Fiscal Year
2002
Total Cost
$253,980
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Vanaja, Donkena Krishna; Grossmann, Michael E; Cheville, John C et al. (2009) PDLIM4, an actin binding protein, suppresses prostate cancer cell growth. Cancer Invest 27:264-72
Zhang, J-S; Gong, A; Young, C Y F (2007) ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in prostate cancer. Oncogene 26:111-22
Wang, Chenguang; Li, Zhiping; Lu, Yinan et al. (2006) Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Proc Natl Acad Sci U S A 103:11567-72
Vanaja, Donkena Krishna; Ballman, Karla V; Morlan, Bruce W et al. (2006) PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer. Clin Cancer Res 12:1128-36
Zhang, Pengju; Zhang, Jianye; Young, Charles Y F et al. (2005) Decoy androgen-responsive element DNA can inhibit androgen receptor transactivation of the PSA promoter gene. Ann Clin Lab Sci 35:278-84
Zhang, Jin-San; Gong, Aiyu; Cheville, John C et al. (2005) AGR2, an androgen-inducible secretory protein overexpressed in prostate cancer. Genes Chromosomes Cancer 43:249-59
Debes, Jose D; Sebo, Thomas J; Heemers, Hannelore V et al. (2005) p300 modulates nuclear morphology in prostate cancer. Cancer Res 65:708-12
Grossmann, Michael E; Madden, Benjamin J; Gao, Fan et al. (2004) Proteomics shows Hsp70 does not bind peptide sequences indiscriminately in vivo. Exp Cell Res 297:108-17
Yuan, Huiqing; Pan, Yunqian; Young, Charles Y F (2004) Overexpression of c-Jun induced by quercetin and resverol inhibits the expression and function of the androgen receptor in human prostate cancer cells. Cancer Lett 213:155-63
Young, Charles Y F; Jatoi, Aminah; Ward, John F et al. (2004) The effects of dietary factors on the androgen receptor and related cellular factors in prostate cancer. Curr Med Chem 11:909-23

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