CYP24 splicing variants are associated with different patterns of constitutive and calcitriol-inducible CYP24 activity in human prostate cancer cell lines

• Published in: Journal of steroid biochemistry and molecular biology Vol. 103; no. 3-5; pp. 334 - 337
• Main Authors: Muindi, Josephia R., Nganga, Alain, Engler, Kristie L., Coignet, Lionel J., Johnson, Candace S., Trump, Donald L.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2007; Elsevier Science
• Subjects: Alternative Splicing - drug effects; Alternative Splicing - genetics; Biological and medical sciences; Calcitriol - pharmacology; Cell Line, Tumor; CYP24 SNPs; Enzyme Activation; Exons - genetics; Gene Expression Regulation, Enzymologic; Genetic Variation - drug effects; Genetic Variation - genetics; Gynecology. Andrology. Obstetrics; Humans; Introns - genetics; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Polymorphism, Single Nucleotide - genetics; Prostate cancer cell lines; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - genetics; Splicing and enzyme activity profile; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vitamin D3 24-Hydroxylase; CYP24 SNPs; Splicing and enzyme activity profile; Prostate cancer cell lines; Human; Urinary system disease; Prostate disease; Splicing; Cholecalciferol(1,25-dihydroxy); Calcitriol; Malignant tumor; Variant; Cell line; Enzymatic activity; Male genital diseases; Prostate cancer; Cancer
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2006.12.060

24-Hydroxylase (CYP24) activity modulates in vitro and in vivo calcitriol metabolism and biologic effects. We have investigated, in human PC3, DU145 and LNCaP prostate cancer cell lines, the relationship of CYP24 single nucleotide polymorphisms (SNPs) and splicing and the variable patterns of baseline and calcitriol-inducible CYP24 activity. DU145 cells exhibit baseline CYP24 activity that is further induced by calcitriol. Baseline and inducible CYP24 activity were barely detectable in LNCaP cells. In PC3, baseline CYP24 activity was undetectable but induced by calcitriol. A different pattern of SNPs was identified at positions 24, 46, 146 and 198 in the intron between exons 9 and 10 of CYP24 gene in each cancer cell line. DU145 displayed baseline CYP24 splicing between exon 9 and exon 11; splicing was only observed in calcitriol treated LNCaP cells. Untreated PC3 had a mixed picture (splicing and no splicing); only the spliced form was seen after calcitriol treatment. These results demonstrate that calcitriol treatment modulates CYP24 splicing, and suggests that differences in CYP24 splicing are associated with different patterns of CYP24 activity.