This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Klokk, T. I. Articles by Saatcioglu, F. Search for Related Content PubMed PubMed Citation Articles by Klokk, T. I. Articles by Saatcioglu, F.

Kallikrein 4 Is a Proliferative Factor that Is Overexpressed in Prostate Cancer

Departments of ¹ Molecular Biosciences, ² Medical Informatics, ³ Surgical Clinic, and ⁴ Pathology; and ⁵ Center for Cancer Biomedicine, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway

Requests for reprints: Fahri Saatcioglu, Department of Molecular Biosciences, PB 1041 Blindern, 0316 Oslo, Norway. Phone: 47-22854569; Fax: 47-22857207; E-mail: fahris{at}imbv.uio.no.

Kallikrein 4 (KLK4) is a member of the human tissue KLK family. Whereas all other KLKs are secreted proteins with extracellular functions, KLK4 is primarily localized to the nucleus, indicating that it has a different function compared with other members of the KLK family. In addition, KLK4 expression is highly enriched in the prostate and is regulated by androgens. Here, we studied the possible functional role of KLK4 in prostate cancer cells and examined its expression at the protein level in prostate cancer specimens. Consistent with its mRNA expression, KLK4 protein is significantly overexpressed in malignant prostate compared with normal prostate. KLK4 expression is predominantly in the nucleus of basal cells in the prostate epithelium in keeping with its distribution in prostate cancer cells in vitro. Furthermore, adenovirus-mediated expression of KLK4 dramatically induces proliferation of prostate cancer cells, at least in part through significant alterations in cell cycle regulatory gene expression. Consistent with these data, small interfering RNA–mediated knockdown of endogenous KLK4 in LNCaP prostate cancer cells inhibits cell growth. These data identify KLK4 as the first member of the KLK family that is a proliferative factor with effects on gene expression and indicate that it may have an important role in prostate cancer development and progression. [Cancer Res 2007;67(11):5221–30]

This article has been cited by other articles:

				Y. J. Arnoldussen, P. I. Lorenzo, M. E. Pretorius, H. Waehre, B. Risberg, G. M. Maelandsmo, H. E. Danielsen, and F. Saatcioglu The Mitogen-Activated Protein Kinase Phosphatase Vaccinia H1-Related Protein Inhibits Apoptosis in Prostate Cancer Cells and Is Overexpressed in Prostate Cancer Cancer Res., November 15, 2008; 68(22): 9255 - 9264. [Abstract] [Full Text] [PDF]

				G. J. Mize, W. Wang, and T. K. Takayama Prostate-Specific Kallikreins-2 and -4 Enhance the Proliferation of DU-145 Prostate Cancer Cells through Protease-Activated Receptors-1 and -2 Mol. Cancer Res., June 1, 2008; 6(6): 1043 - 1051. [Abstract] [Full Text] [PDF]

				A. J. Ramsay, Y. Dong, M. L. Hunt, M. Linn, H. Samaratunga, J. A. Clements, and J. D. Hooper Kallikrein-related Peptidase 4 (KLK4) Initiates Intracellular Signaling via Protease-activated Receptors (PARs): KLK4 AND PAR-2 ARE CO-EXPRESSED DURING PROSTATE CANCER PROGRESSION J. Biol. Chem., May 2, 2008; 283(18): 12293 - 12304. [Abstract] [Full Text] [PDF]