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Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
a Address for correspondence: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada. E-mail ediamandis{at}mtsinai.on.ca
Background: Prostate-specific antigen (PSA) is a valuable prostatic cancer biomarker that is now widely used for population screening, diagnosis, and monitoring of patients with prostate cancer. Despite the voluminous literature on this biomarker, relatively few reports have addressed the issue of its physiological function and its connection to the pathogenesis and progression of prostate and other cancers.
Approach: I here review literature dealing with PSA physiology and pathobiology and discuss reports that either suggest that PSA is a beneficial molecule with tumor suppressor activity or that PSA has deleterious effects in prostate, breast, and possibly other cancers.
Content: The present scientific literature on PSA physiology and pathobiology is confusing. A group of reports have suggested that PSA may act as a tumor suppressor, a negative regulator of cell growth, and an apoptotic molecule, whereas others suggest that PSA may, through its chymotrypsin-like activity, promote tumor progression and metastasis.
Summary: The physiological function of PSA is still not well understood. Because PSA is just one member of the human kallikrein gene family, it is possible that its biological functions are related to the activity of other related kallikreins. Only when the physiological functions of PSA and other kallikreins are elucidated will we be able to explain the currently apparently conflicting experimental data.
The following articles in journals at HighWire Press have cited this article:
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  V. D'Arcy, Z. K. Abdullaev, N. Pore, F. Docquier, V. Torrano, I. Chernukhin, M. Smart, D. Farrar, M. Metodiev, N. Fernandez, et al. The Potential of BORIS Detected in the Leukocytes of Breast Cancer Patients as an Early Marker of Tumorigenesis. Clin. Cancer Res., October 15, 2006; 12(20): 5978 - 5986. [Abstract] [Full Text] [PDF]
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 K. El-Bayoumy, J. P. Richie Jr., T. Boyiri, D. Komninou, B. Prokopczyk, N. Trushin, W. Kleinman, J. Cox, B. Pittman, and S. Colosimo Influence of Selenium-enriched Yeast Supplementation on Biomarkers of Oxidative Damage and Hormone Status in Healthy Adult Males: A Clinical Pilot Study Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1459 - 1465. [Abstract] [Full Text] [PDF]
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 E. P. Diamandis and G. M. Yousef Human Tissue Kallikreins: A Family of New Cancer Biomarkers Clin. Chem., August 1, 2002; 48(8): 1198 - 1205. [Abstract] [Full Text] [PDF]
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P. Niemela, J. Lovgren, M. Karp, H. Lilja, and K. Pettersson Sensitive and Specific Enzymatic Assay for the Determination of Precursor Forms of Prostate-specific Antigen after an Activation Step Clin. Chem., August 1, 2002; 48(8): 1257 - 1264. [Abstract] [Full Text] [PDF]
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B. R. Grzeda, T. Le Bui, C. N. Warner, T. L. Pirucki, L. M. Dewey, M. Babich, and J. A. Maggiore Measurement of Prostate-specific Antigen by Use of a Novel Blood Collection and Analytical System Clin. Chem., August 1, 2002; 48(8): 1272 - 1278. [Abstract] [Full Text] [PDF]
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 A. David, N. Mabjeesh, I. Azar, S. Biton, S. Engel, J. Bernstein, J. Romano, Y. Avidor, T. Waks, Z. Eshhar, et al. Unusual Alternative Splicing within the Human Kallikrein Genes KLK2 and KLK3 Gives Rise to Novel Prostate-specific Proteins J. Biol. Chem., May 10, 2002; 277(20): 18084 - 18090. [Abstract] [Full Text] [PDF]
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F. J. Meng, A. Shan, L. Jin, and C. Y. F. Young The Expression of a Variant Prostate-specific Antigen in Human Prostate Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 305 - 309. [Abstract] [Full Text] [PDF]
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 M. E. Taplin and S.-M. Ho The Endocrinology of Prostate Cancer J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3467 - 3477. [Full Text] [PDF]
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 G. M. Yousef and E. P. Diamandis The New Human Tissue Kallikrein Gene Family: Structure, Function, and Association to Disease Endocr. Rev., April 1, 2001; 22(2): 184 - 204. [Abstract] [Full Text]
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