Document Detail


Induction of 3beta-hydroxysteroid dehydrogenase/isomerase type 1 expression by interleukin-4 in human normal prostate epithelial cells, immortalized keratinocytes, colon, and cervix cancer cell lines.
MedLine Citation:
PMID:  10499513     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) isoenzymes catalyze an essential step in the formation of all classes of active steroid hormones. In humans there are two 3beta-HSD isoenzymes, the type 1 gene being predominantly expressed in the placenta and peripheral tissues, whereas the type 2 gene is the predominant 3beta-HSD expressed in the adrenal glands and gonads. We have recently showed that interleukin (IL)-4 and IL-13 induce 3beta-HSD type 1 gene expression in human breast cancer cell lines as well as in normal human mammary epithelial cells. The present study was designed to investigate whether such a cytokine-induced 3beta-HSD type 1 expression would also be observed in cell types derived from other peripheral sex steroid target tissues. To gain further knowledge about the molecular mechanism of IL-4 action, we have studied whether the induction of 3beta-HSD type 1 expression in IL-4-responsive cell types would always be associated with the activation of Stat6, a member of the Signal Transducers and Activators of Transcription (STAT) gene family. Stat6 is recognized as the principal transcription factor mediating the effects of IL-4. In normal human prostate epithelial cells (PrEC), no 3beta-HSD activity was detectable under basal culture conditions, while exposure to IL-4 or IL-13 caused a potent induction of this activity. This effect results from a rapid induction of 3beta-HSD type 1 messenger RNA levels as determined by Northern blot and RT-PCR analyses. Furthermore, IL-4 and IL-13 also increased 3beta-HSD type 1 gene expression in human HaCaT immortalized keratinocytes, ME-180 cervix cancer cells, HT-29 colon cancer cells as well as in BT-20 and ZR-75-1 breast cancer cells. However, IL-4 and IL-13 failed to modulate the 3beta-HSD type 1 expression in human LnCAP and PC-3 prostate cancer cells, Caco-2 colon cancer cells as well as in JAR and JEG-3 choriocarcinoma cell lines. The DNA-binding activity of Stat6 was activated after a 30-min exposure to IL-4 in PrEC and in all the cell types where IL-4 induced 3beta-HSD expression, but not in those that failed to respond to IL-4. Our data therefore suggest that IL-4 and IL-13 may play a role in the biosynthesis of active sex steroids from the inactive adrenal steroid dehydroepiandrosterone, not only in breast cells but also in various cell types derived from peripheral target tissues, such as normal human prostate epithelial cells, immortalized keratinocytes, as well as colon and cervix cancer cell lines. Our data also demonstrates that the stimulatory effect of IL-4 was always associated with the activation of Stat6, thus supporting the essential role of Stat6 in this induction of 3beta-HSD type 1 gene expression.
Authors:
S Gingras; J Simard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  140     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-12     Completed Date:  1999-10-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4573-84     Citation Subset:  AIM; IM    
Affiliation:
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University, Québec City, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxysteroid Dehydrogenases / genetics,  metabolism*
Cell Line, Transformed
Colonic Neoplasms / enzymology*,  metabolism
Enzyme Induction / drug effects
Epithelial Cells / enzymology,  metabolism
Female
Humans
Interleukin-13 / pharmacology
Interleukin-4 / pharmacology*
Isoenzymes / genetics,  metabolism
Isomerases / metabolism
Keratinocytes / enzymology*,  metabolism
Male
Prostate / cytology,  enzymology*,  metabolism
RNA, Messenger / metabolism
Reference Values
STAT6 Transcription Factor
Trans-Activators / metabolism
Uterine Cervical Neoplasms / enzymology*,  metabolism
Chemical
Reg. No./Substance:
0/Interleukin-13; 0/Isoenzymes; 0/RNA, Messenger; 0/STAT6 Transcription Factor; 0/STAT6 protein, human; 0/Trans-Activators; 207137-56-2/Interleukin-4; EC 1.1.-/3-Hydroxysteroid Dehydrogenases; EC 5.-/Isomerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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