• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of gutGutView this articleSubmit a manuscriptReceive email alertsContact usBMJ
Gut. Feb 1995; 36(2): 255–258.
PMCID: PMC1382413

1,25-Dihydroxyvitamin D3 and retinoid X receptor expression in human colorectal neoplasms.

Abstract

Epidemiological studies suggest that 1,25-dihydroxyvitamin D3 (D3) protects against colorectal carcinogenesis. Animal and in vitro studies show an antiproliferative effect of D3 in a variety of tumours including those of large bowel origin. D3 actions are mediated by D3 receptors (VDR) alone or by VDR in conjunction with retinoid X receptors (RXRs) in all D3 responsive tissues. The expression of mRNAs encoding VDR and RXRs in normal and malignant human colorectum was determined. Full length VDR (4.6 kB), RXR alpha (5.5 kB), and RXR gamma (3.5 and 7 kB) mRNAs were expressed in all tissues, but RXR beta mRNA was not expressed in any. VDR expression was reduced in 12 carcinomas relative to paired normal mucosa, and RXR alpha expression was reduced in nine. There was no correlation between VDR or RXR alpha expression and the site, grade of differentiation, or Dukes's staging of the tumour. The finding of persistent VDR and RXR coexpression in all colorectal tumours provides a rational basis for exploring a role for D3 in the treatment of colorectal malignancy.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bikle DD. Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential. Endocr Rev. 1992 Nov;13(4):765–784. [PubMed]
  • Lian JB, Stein GS, Bortell R, Owen TA. Phenotype suppression: a postulated molecular mechanism for mediating the relationship of proliferation and differentiation by Fos/Jun interactions at AP-1 sites in steroid responsive promoter elements of tissue-specific genes. J Cell Biochem. 1991 Jan;45(1):9–14. [PubMed]
  • Colston KW, Berger U, Coombes RC. Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet. 1989 Jan 28;1(8631):188–191. [PubMed]
  • Garland C, Shekelle RB, Barrett-Connor E, Criqui MH, Rossof AH, Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985 Feb 9;1(8424):307–309. [PubMed]
  • Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet. 1989 Nov 18;2(8673):1176–1178. [PubMed]
  • Pence BC, Buddingh F. Inhibition of dietary fat-promoted colon carcinogenesis in rats by supplemental calcium or vitamin D3. Carcinogenesis. 1988 Jan;9(1):187–190. [PubMed]
  • Sitrin MD, Halline AG, Abrahams C, Brasitus TA. Dietary calcium and vitamin D modulate 1,2-dimethylhydrazine-induced colonic carcinogenesis in the rat. Cancer Res. 1991 Oct 15;51(20):5608–5613. [PubMed]
  • Llor X, Jacoby RF, Teng BB, Davidson NO, Sitrin MD, Brasitus TA. K-ras mutations in 1,2-dimethylhydrazine-induced colonic tumors: effects of supplemental dietary calcium and vitamin D deficiency. Cancer Res. 1991 Aug 15;51(16):4305–4309. [PubMed]
  • Eisman JA, Barkla DH, Tutton PJ. Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res. 1987 Jan 1;47(1):21–25. [PubMed]
  • Brehier A, Thomasset M. Human colon cell line HT-29: characterisation of 1,25-dihydroxyvitamin D3 receptor and induction of differentiation by the hormone. J Steroid Biochem. 1988 Feb;29(2):265–270. [PubMed]
  • Tanaka Y, Bush KK, Klauck TM, Higgins PJ. Enhancement of butyrate-induced differentiation of HT-29 human colon carcinoma cells by 1,25-dihydroxyvitamin D3. Biochem Pharmacol. 1989 Nov 1;38(21):3859–3865. [PubMed]
  • Giuliano AR, Franceschi RT, Wood RJ. Characterization of the vitamin D receptor from the Caco-2 human colon carcinoma cell line: effect of cellular differentiation. Arch Biochem Biophys. 1991 Mar;285(2):261–269. [PubMed]
  • Shabahang M, Buras RR, Davoodi F, Schumaker LM, Nauta RJ, Evans SR. 1,25-Dihydroxyvitamin D3 receptor as a marker of human colon carcinoma cell line differentiation and growth inhibition. Cancer Res. 1993 Aug 15;53(16):3712–3718. [PubMed]
  • Ozono K, Sone T, Pike JW. The genomic mechanism of action of 1,25-dihydroxyvitamin D3. J Bone Miner Res. 1991 Oct;6(10):1021–1027. [PubMed]
  • Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. [PubMed]
  • Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature. 1992 Jan 30;355(6359):446–449. [PubMed]
  • Yu VC, Delsert C, Andersen B, Holloway JM, Devary OV, När AM, Kim SY, Boutin JM, Glass CK, Rosenfeld MG. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell. 1991 Dec 20;67(6):1251–1266. [PubMed]
  • Williams GR, Brent GA. Specificity of nuclear hormone receptor action: who conducts the orchestra? J Endocrinol. 1992 Nov;135(2):191–194. [PubMed]
  • Green S. Nuclear hormone receptors. Promiscuous liaisons. Nature. 1993 Feb 18;361(6413):590–591. [PubMed]
  • Carlberg C, Bendik I, Wyss A, Meier E, Sturzenbecker LJ, Grippo JF, Hunziker W. Two nuclear signalling pathways for vitamin D. Nature. 1993 Feb 18;361(6413):657–660. [PubMed]
  • Baker AR, McDonnell DP, Hughes M, Crisp TM, Mangelsdorf DJ, Haussler MR, Pike JW, Shine J, O'Malley BW. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U S A. 1988 May;85(10):3294–3298. [PMC free article] [PubMed]
  • Mangelsdorf DJ, Ong ES, Dyck JA, Evans RM. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature. 1990 May 17;345(6272):224–229. [PubMed]
  • Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev. 1992 Mar;6(3):329–344. [PubMed]
  • Thomas MG, Tebbutt S, Williamson RC. Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. Gut. 1992 Dec;33(12):1660–1663. [PMC free article] [PubMed]
  • Berger U, Wilson P, McClelland RA, Colston K, Haussler MR, Pike JW, Coombes RC. Immunocytochemical detection of 1,25-dihydroxyvitamin D receptors in normal human tissues. J Clin Endocrinol Metab. 1988 Sep;67(3):607–613. [PubMed]
  • Meggouh F, Lointier P, Saez S. Sex steroid and 1,25-dihydroxyvitamin D3 receptors in human colorectal adenocarcinoma and normal mucosa. Cancer Res. 1991 Feb 15;51(4):1227–1233. [PubMed]
  • Decarli A, Liati P, Negri E, Franceschi S, La Vecchia C. Vitamin A and other dietary factors in the etiology of esophageal cancer. Nutr Cancer. 1987;10(1-2):29–37. [PubMed]
  • Mano H, Ozawa T, Takeyama K, Yoshizawa Y, Kojima R, Kato S, Masushige S. Thyroid hormone affects the gene expression of retinoid X receptors in the adult rat. Biochem Biophys Res Commun. 1993 Mar 31;191(3):943–949. [PubMed]
  • Fuqua SA, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malley BW, McGuire WL. Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res. 1991 Jan 1;51(1):105–109. [PubMed]
  • Arbour NC, Prahl JM, DeLuca HF. Stabilization of the vitamin D receptor in rat osteosarcoma cells through the action of 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1993 Oct;7(10):1307–1312. [PubMed]
  • Colston KW. New concepts in hormone receptor action. Lancet. 1993 Jul 10;342(8863):67–68. [PubMed]
  • MacDonald PN, Dowd DR, Nakajima S, Galligan MA, Reeder MC, Haussler CA, Ozato K, Haussler MR. Retinoid X receptors stimulate and 9-cis retinoic acid inhibits 1,25-dihydroxyvitamin D3-activated expression of the rat osteocalcin gene. Mol Cell Biol. 1993 Sep;13(9):5907–5917. [PMC free article] [PubMed]
  • Binderup L, Latini S, Binderup E, Bretting C, Calverley M, Hansen K. 20-epi-vitamin D3 analogues: a novel class of potent regulators of cell growth and immune responses. Biochem Pharmacol. 1991 Sep 27;42(8):1569–1575. [PubMed]
  • Binderup L, Bramm E. Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo. Biochem Pharmacol. 1988 Mar 1;37(5):889–895. [PubMed]

Articles from Gut are provided here courtesy of BMJ Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...