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Understanding Prostate Gene Expression
Posted November 21, 2001
Peter S. Nelson, M.D., Fred Hutchinson Cancer Center, University of Washington

The key to understanding human health and disease is found within each cell in the body and is represented by the complete set of genes that are expressed in that cell. Because each cell type in the body expresses a different set of genes, a catalogue of genes expressed in a particular normal cell type is necessary before those genes whose expression changes during disease can be identified. Two awards made to the Fred Hutchinson Cancer Center at the University of Washington are supporting the development and use of a comprehensive database of gene expression called the Prostate Expression Database (PEDB). This genetic resource capitalizes on the results of the Human Genome Project and uses advanced molecular biology and bioinformatics techniques and approaches to catalogue the thousands of genes that are expressed in prostate cells. In essence, this integrated database provides a blueprint of gene expression in normal prostate cells and can track changes in that blueprint that are associated with the transformation of cells from normal to cancerous. In addition to developing this resource, these investigators are focused on using it to identify differences that may occur in the androgen receptor pathway in prostate cells as cells transform from normal to cancerous. Using the PEBD and associated techniques, these researchers identified a novel prostate-specific gene that is related to androgen metabolism and that is highly expressed in primary and metastatic prostate carcinoma. The PEBD developed by the Fred Hutchinson group is rapidly becoming an important international genetic resource. It is being used by prostate cancer researchers worldwide to identify, study, and obtain prostate associated molecules for detailed molecular, epidemiological, diagnostic, and therapeutic uses.

Publications:

Nelson PS, Han D, Rochan Y, Corthais GL, Lin B, Monson A, NguyenV, Franza BR, Plymate SR, Aebersold R, and Hood L. 2000. Comprehensive analyses of prostate gene expression: convergence of expressed sequence tag databases, transcript profiling, and proteomics. Electrophoresis 21: 1823-1831.

Grouse LH, Munson PJ, and Nelson PS. 2001. Sequence databases and microarrays as tools for identifying prostate cancer biomarkers. J. Urology 57 (Suppl 4A):154-159.

Link:

Abstract: The Prostate Expression Database: PEDB

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Green Tea Inhibits Prostate Cancer Cell Growth and Metastasis
Posted October 8, 2001
Hasan Mukhtar, Ph.D., Departments of Dermatology and Radiology, Case Western Reserve University and The Research Institute of University Hospitals of Cleveland, Cleveland, Ohio
Fiscal Year 2000

Treatment of prostate cancer is currently limited to surgery, radiation therapy, hormone therapy, or "watchful waiting," depending upon the age and overall health of the man at the time of diagnosis. Preventive therapies, especially natural, nutritional therapies that could inhibit prostate cancer development, slow tumor growth, and limit the spread of more advanced prostate tumors, could have a major impact on the incidence of the disease in men. Prostate Cancer Research Program grant recipient Dr. Hasan Mukhtar from Case Western Reserve University has studied the effects of green tea, a popular drink throughout Asia that has an increasing popularity in Western countries, on cancer prevention. Specific chemical components of green tea, called polyphenolics, were separated from green tea. Using a mouse model that closely mimics prostate cancer in humans (called TRAMP for transgenic adenocarcinoma of the mouse prostate), the polyphenolics were given to the mice at a dose equivalent to six cups of green tea a day. TRAMP mice that did not receive the green tea compounds developed prostate cancer by 20 weeks of age, and by 32 weeks, all of the untreated TRAMP mice had metastatic prostate tumors. However, treated TRAMP mice developed prostate tumors at a much lower rate, and when tumors did develop in the mice none spread to other organs. The green tea polyphenols also increased the average survival time for the TRAMP mice from 42 weeks without treatment to 68 weeks with the green tea therapy. Future research with these compounds may provide a treatment that could slow or possibly even prevent the development of prostate cancer.

Publications:

Gupta S, Hastak K, Ahmad N, Lewin JS, and Mukhtar H. 2001. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proceedings of the National Academy of Science, 98(18):10350-10355.

Link:

Abstract: Green Tea in Prevention and Therapy of Prostate Cancer

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Identifying Aggressive Prostate Cancer Tumors
Posted August 14, 2001
Stephen J. Doxsey, Ph.D., German Pihan, M.D., University of Massachusetts Medical Center
Fiscal Year 2000

Prostate Specific Antigen (PSA) is a protein produced by the prostate gland that becomes elevated in prostate cancers. While most prostate cancer cases can be detected by a blood test for PSA, this test does not distinguish cancers that progress rapidly (aggressive tumors) from those that progress slowly. Thus, it is very important to develop a test that can distinguish between these two types of tumors. Prostate Cancer Research Program Dual Phase researchers at the University of Massachusetts Medical Center are studying the role of centrosomes (complex structures that play a critical role in cell division and organization) in aggressive prostate cancer. These investigators were among the first to discover that the number of centrosomes and their structures are abnormal in all cancers, including prostate cancer. During the second phase of this study, the investigators will determine whether these centrosome abnormalities can be used to predict whether or not a tumor is aggressive. This study is expected to lead to the development of a simple blood test that can predict how a tumor may behave over time. This will improve the ability to identify patients with aggressive disease and help design new therapies.

Publications:

Doxsey SJ. Centrosomes as command centres for cellular control. Nature Cell Biology 2001, May 3 (5):E105-8.

Pihan GA, Purohit A, Wallace J, Malhotra R, Liotta L, Doxsey SJ. Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. Cancer Research 2001, Mar 1, 61(5):2212-9.

Link:

Abstract: Centrosome Defects, Genetic Instability and Prostate Cancer Progression

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