Carcinogenesis Advance Access published online on January 23, 2004
Carcinogenesis, doi:10.1093/carcin/bgh086
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARCINOGENESIS
1 Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Public Health Sciences, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
* Corresponding author. E-mail: ckoumeni{at}wfubmc.edu.
Received 26 August 2003
; revised 16 December 2003
; accepted 10 January 2004
The steroid hormone 1,25-dihydroxyvitamin D3, (1,25(OH)2D3, calcitriol), the active metabolite of Vitamin D, exerts pleiotropic antitumor effects against several malignancies. However, the clinical use of this hormone is limited by hypercalcemia. 25-hydroxyvitamin D3, the prohormone of 1,25(OH)2D3, is hydroxylated to the active hormone by the enzyme 25-hydroxyvitamin-1-
Pancreatic cancer cells express 25-Hydroxyvitamin D-1
-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3
2 Department of Radiation Oncology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
3 Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
4 Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Department of Urology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
5 Department of Pathology, Comprehensive Cancer Center of Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
6 Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Massachusetts 02118, USA
7 Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33136, USA
-hydroxylase [1(OH)ase]. 1(OH)ase is found primarily in the kidney, but also is expressed in the prostate, colon, and other tissues. Using immunohistochemistry, we report that 1(OH)ase is highly expressed in both normal and malignant pancreatic tissue. Expression of this enzyme and enzymatic activity were also detected in 4 pancreatic tumor cell lines. 25(OH)D3 inhibited the growth of three of four pancreatic cell lines in a manner that correlated with the level of induction of the cyclin dependent kinase inhibitors p21 and p27 and with the induction of cell cycle arrest at the G1/S checkpoint. The growth of a cell line stably transfected with a mutant Ki-ras allele and of a second cell line with an endogenous Ki-ras activating mutation was also inhibited by 25(OH)D3, indicating that activating Ki-Ras mutations, which occur in almost 90% of pancreatic adenocarcinomas, do not interfere with the growth-inhibitory effects of 25(OH)D3. The expression of 1(OH)ase in normal and malignant pancreatic tissue and the antiproliferative effects of the prohormone in these cells, suggest that 25(OH)D3 may offer possible therapeutic and chemopreventive options for pancreatic cancer.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. VIETH How to Optimize Vitamin D Supplementation to Prevent Cancer, Based on Cellular Adaptation and Hydroxylase Enzymology Anticancer Res, September 1, 2009; 29(9): 3675 - 3684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. PETERLIK, W. B. GRANT, and H. S. CROSS Calcium, Vitamin D and Cancer Anticancer Res, September 1, 2009; 29(9): 3687 - 3698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Z. Stolzenberg-Solomon, R. B. Hayes, R. L. Horst, K. E. Anderson, B. W. Hollis, and D. T. Silverman Serum Vitamin D and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial Cancer Res., February 15, 2009; 69(4): 1439 - 1447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D Davis Vitamin D and cancer: current dilemmas and future research needs Am. J. Clinical Nutrition, August 1, 2008; 88(2): 565S - 569S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Driel, M. Koedam, C. J. Buurman, M. Hewison, H. Chiba, A. G. Uitterlinden, H. A. P. Pols, and J. P. T. M. van Leeuwen Evidence for auto/paracrine actions of vitamin D in bone: 1{alpha}-hydroxylase expression and activity in human bone cells FASEB J, November 1, 2006; 20(13): 2417 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Z. Stolzenberg-Solomon, R. Vieth, A. Azad, P. Pietinen, P. R. Taylor, J. Virtamo, and D. Albanes A Prospective Nested Case-Control Study of Vitamin D Status and Pancreatic Cancer Risk in Male Smokers Cancer Res., October 15, 2006; 66(20): 10213 - 10219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. G. Skinner, D. S. Michaud, E. Giovannucci, W. C. Willett, G. A. Colditz, and C. S. Fuchs Vitamin d intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol. Biomarkers Prev., September 1, 2006; 15(9): 1688 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Dusso, A. J. Brown, and E. Slatopolsky Vitamin D Am J Physiol Renal Physiol, July 1, 2005; 289(1): F8 - F28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Townsend, C. M. Banwell, M. Guy, K. W. Colston, J. L. Mansi, P. M. Stewart, M. J. Campbell, and M. Hewison Autocrine Metabolism of Vitamin D in Normal and Malignant Breast Tissue Clin. Cancer Res., May 1, 2005; 11(9): 3579 - 3586. [Abstract] [Full Text] [PDF]
|
|