Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue.
1,25(OH)2D3 suppresses proliferation and induces differentiation in various cell types, including epithelial cells. Recently, extrarenal activity of 1alpha-hydroxylase for 25(OH)D3 has been reported in various cell types including macrophages, keratinocytes and prostate and colon cancer cells. The aim of this study was to analyze the expression of 1alpha-hydroxylase for 25-hydroxyvitamin D3 in normal cervical samples and in cervical cancer, in order to investigate whether cervical tissue possesses the capacity to produce 1,25(OH)2D3 from 25(OH)D3, indicating that 1,25(OH)2D3 may be a locally produced hormone that controls proliferation in cervical tissue and that alterations in local production of 1,25(OH)2D3 may be involved in tumourigenesis of cervical cancer.


METHODS
RNA was extracted from normal cervical tissue (n=4), cervical carcinomas (n=8) and HeLa cells using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR.


RESULTS
mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in more than 50% of samples analyzed in normal cervical tissue and in cervical cancer with no visible difference between either group. mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in HeLa cells as well.


CONCLUSIONS
25(OH)D3-1alpha-hydroxylase is expressed in normal cervical tissue, in cervical cancer and in HeLa cells. Thus, normal cervical and cervical cancer cells seem to be able to synthesize 1alpha, 25(OH)2D3 that may be of significant importance for the growth control in normal and malignant cervical tissue. Normal cervical tissue and cervical cancer cells may be new targets for cancer prevention or cancer treatment with precursors of biologically active vitamin D analogues.
Friedrich
Michael
M
Department of Gynecology and Obstetrics, University of Saarland, Homburg/Saar, Germany. mfried@med-fr.uni-sb.de
Villena-Heinsen
Carlos
C
Axt-Fliedner
Roland
R
Meyberg
Roland
R
Tilgen
Wolfgang
W
Schmidt
Werner
W
Reichrath
Jörg
J
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis* / Q000235:genetics; D000230:Adenocarcinoma / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D002584:Cervix Uteri / Q000201:enzymology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
D012333:RNA, Messenger; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase