Cent Eur J Public Health 2007, 15(1):3-6 | DOI: 10.21101/cejph.a3412

Role of Retinoids and their Cognate Nuclear Receptors in Breast Cancer Chemoprevention

Július Brtko
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic

Retinoids are natural and synthetic compounds related to retinoic acid that act through interaction with two basic types of nuclear receptors: retinoic acid receptors (RARα, RARβ and RARγ) and retinoid X receptors (RXRα, RXRβ and RXRγ) as ligand-activated, DNA-binding, transacting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Function of retinoids in organisms affecting broad spectrum of various biochemical and molecular biology reactions is unimaginable without fully functional nuclear receptors - retinoid inducible transcription factors. Retinoic acids exert tumour-suppressive activity due to their antiproliferative and apoptosis-inducing effects. A number of novel retinoids and rexinoids acting through cognate nuclear receptors have been tested both in vitro and in vivo, using cell culture or animal models for breast cancer.
This article briefly summarizes the role and properties of nuclear retinoid/rexinoid receptors as well as selected effects of retinoic acids or selected synthetic retinoids and rexinoids with respect to their potential use in chemoprevention of breast cancer.

Keywords: retinoids, rexinoids, nuclear retinoid acid receptors, prevention of breast cancer, regulation of gene transcription

Received: September 6, 2006; Revised: October 26, 2006; Accepted: October 26, 2006; Published: March 1, 2007  Show citation

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Brtko J. Role of Retinoids and their Cognate Nuclear Receptors in Breast Cancer Chemoprevention. Cent Eur J Public Health. 2007;15(1):3-6. doi: 10.21101/cejph.a3412. PubMed PMID: 17491551.
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References

  1. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005 Mar;16(3):481-8. Go to original source... Go to PubMed...
  2. BaoT, ProwellT, StearnsV. Chemoprevention of breast cancer: tamoxifen, raloxifene, and beyond. Am J Ther. 2006 Jul-Aug;13(4):337-48. Go to original source... Go to PubMed...
  3. Lotan R. Retinoids and apoptosis: implication for cancer chemoprevention and therapy. J Natl Cancer Inst. 1995 Nov 15;87(22):1655-7. Go to original source... Go to PubMed...
  4. Hinds TS, West WL, Knight EM. Carotenoids and retinoids: a review of research, clinical, and public health applications. J Clin Pharmacol. 1997 Jul;37(7):551-8. Go to original source... Go to PubMed...
  5. Nagpal S, Friant S, Nakshatri H, Chambon P. RARs and RXRs: evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. EMBO J. 1993 Jun;12(6):2349-60. Go to original source...
  6. Mader S, Leroy P, Chen JY, Chambon P. Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors. J Biol Chem. 1993 Jan 5;268(1):591-600. Go to original source...
  7. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J. 1996 Jul;10(9):940-54. Go to original source... Go to PubMed...
  8. Crowe DL. Receptor selective synthetic retinoids as potential cancer chemotherapy agents. Curr Cancer Drug Targets. 2002 Mar;2(1):7786. Go to original source... Go to PubMed...
  9. Sun SY, Lotan R. Retinoids and their receptors in cancer development and chemoprevention. Crit Rev Oncol Hematol. 2002 Jan;41(1):41-55. Go to original source... Go to PubMed...
  10. Freedman LP. Increasing the complexity of coactivation in nuclear receptor signaling. Cell. 1999 Apr 2;97(1):5-8. Go to original source... Go to PubMed...
  11. Mukherjee R, Davies PJ, Crombie DL, Bischoff ED, Cesario RM, Jow L, et al. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature. 1997 Mar 27;386(6623):407-10. Go to original source... Go to PubMed...
  12. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995 Dec 15;83(6):841-50. Go to original source... Go to PubMed...
  13. Willy PJ, Mangelsdorf DJ. Nuclear orphan receptors: the search for novel ligands and signaling pathways. In: O'Malley BW, editor. Hormones and Signaling, Vol. 1. San Diego: Academic Press; 1998. p. 307-58. Go to original source...
  14. Brtko J, Thalhamer J. Renaissance of the biologically active vitamin A derivatives: established and novel directed therapies for cancer and chemoprevention. Curr Pharm Des. 2003;9(25):2067-77. Go to original source... Go to PubMed...
  15. Chambon P. The nuclear receptor superfamily: a personal retrospect on the first two decades. Mol Endocrinol. 2005 Jun;19(6):1418-28. Go to original source... Go to PubMed...
  16. Sporn MB, Suh N. Chemoprevention of cancer. Carcinogenesis. 2000 Mar;21(3):525-30. Go to original source... Go to PubMed...
  17. Marth C, Bock G, Daxenbichler G. Effect of 4-hydroxyphenylretinamide and retinoic acid on proliferation and cell cycle of cultured human breast cancer cells. J Natl Cancer Inst. 1985 Nov;75(5):871-5. Go to original source... Go to PubMed...
  18. Fontana JA, Mezu AB, Copper BN, Miranda D. Retinoid modulation of estradiol-stimulated growth and of protein synthesis and secretion in human breast carcinoma cells. Cancer Res. 1990 Apr 1;50(7):1997-2002.
  19. Mehta RG. Experimental basis for the prevention of breast cancer. Eur J Cancer. 2000 Jun;36(10):1275-82. Go to original source... Go to PubMed...
  20. Liska J, Galbavy S, Macejova D, Zlatos J, Brtko J. Histopathology of mammary tumors in female rats treated with 1-methyl-1-nitrosourea. Endocr Regul. 2000 Jun;34(2):91-6. Go to PubMed...
  21. Liska J, Galbavy S, Zlatos J, Macejova D, Micincova M, Brtko J. Mammary tumors in female rats developed after 1-methyl-1nitrosourea treatment. Biologia. 2000;55 Suppl 8:63-7.
  22. Macejova D, Dvorcakova M, Weiss R, Scheiblhofer S, Mostbock S, Liska J, et al. Reduction of 1-methyl-1-nitrosourea-insuced mammary gland carcinoma by in vivo application of immunostimulatory CpG motifs in Sprague-Dawley rats. Gen Physiol Biophys. 2001 Dec;20(4):445-8. Go to PubMed...
  23. Macejova D, Baranova M, Liska J, Brtko J. Expression of nuclear hormone receptors, their coregulators and type I iodothyronine 5'-deiodinase gene in mammary tissue of nonlactating and postlactating rats. Life Sci. 2005 Sep 30;77(20):2584-93. Go to original source... Go to PubMed...
  24. Macejova D, Radikova Z, Macho L, Liska J, Brtko J. MNU-induced carcinogenesis of rat mammary gland: effect of thyroid hormone on expression of retinoic acid receptors in tumours of mammary gland. Mol Cell Endocrinol. 2005 Dec 1;244(1-2):47-56. Go to original source... Go to PubMed...
  25. Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66 (7):606-30. Go to original source... Go to PubMed...
  26. Hudecova S, Stefanik P, Macejova D, Brtko J, Krizanova O. Retinoic acid increased expression of the Na+/Ca2+ exchanger in the heart and brain. Gen Physiol Biophys. 2004 Dec;23(4):417-22. Go to PubMed...
  27. Gottardis MM, Bischoff ED, Shirley MA, Wagoner MA, Lamph WW, Heyman RA. Chemoprevention of mammary carcinoma by LGD1069 (Targretin): an RXR-selective ligand. Cancer Res. 1996 Dec 15;56(24):5566-70.
  28. Wu K, Kim HT, Rodriquez JL, Hilsenbeck SG, Moshin SK, Xu XC, et al. Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069. Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):467-74.
  29. Moon RC, Constantinou AI. Dietary retinoids and carotenoids in rodent models of mammary tumorigenesis. Breast Cancer Res Treat. 1997 NovDec;46(2-3):181-9. Go to original source... Go to PubMed...
  30. Elstner E, Williamson EA, Zang C, Fritz J, Heber D, Fenner M, et al. Novel therapeuric approach: ligands for PPARγ and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells. Breast Cancer Res Treat. 2002 Jul;74(2):155-65. Go to original source... Go to PubMed...
  31. Zhang XK, Liu L, Lee MO. Retinoid receptors in human lung and breast cancer. Mutat Res. 1996 Feb 19;350(1):267-77. Go to original source... Go to PubMed...
  32. Zujewski J, Pai L, Wakefield L, Giusti R, Dorr FA, Flanders C, et al. Tamoxifen and fenretinide in women with metastatic breast cancer. Breast Cancer Res Treat. 1999 Oct;57(3):277-83. Go to original source... Go to PubMed...
  33. Singletary E, Lieberman R, Atkinson N, Sneige N, Sahin A, Tolley S, et al. Novel translational model for breast cancer chemoprevention study: accrual to a presurgical intervention with tamoxifen and N-[4-hydroxyphenyl] retinamide. Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1087-90.
  34. Sporn MB. Retinoids and demethylating agents - looking for partners. J Natl Cancer Inst. 2000 May 17;92(10):780-1. Go to original source... Go to PubMed...
  35. Widschwendter M, Berger J, Hermann M, Muller HM, Amberger A, Zeschnigk M, et al. Methylation and silencing of the retinoic acid receptor-β2 gene in breast cancer. J Natl Cancer Inst. 2000 May 17;92(10): 826-32. Go to original source... Go to PubMed...
  36. Lin B, Chen GQ, Xiao D, Kolluri SK, Cao X, Su H, et al. Orphan receptor COUP-TF is required for induction of retinoic acid receptor β, growth inhibition, and apoptosis by retinoic acid in cancer cells. Mol Cell Biol. 2000 Feb;20(3):957-70. Go to original source... Go to PubMed...
  37. Mostbock S, Macejova D, Baranova M, Weiss R, Scheiblhofer S, Verwanger T, et al.Analysis of altered gene expression profiles in retinoic acid or CpG-treated Sprague-Dawley rats with MNU-induced mammary adenocarcinoma by cDNA macro array. Gen Physiol Biophys. 2003 Mar;22(1):129-33. Go to PubMed...
  38. Zanardi S, Serrano D,ArgustiA, Barile M, Puntoni M, DecensiA. Clinical trials with retinoids for breast cancer chemoprevention. Endocr Relat Cancer. 2006 Mar;13(1):51-68. Go to original source... Go to PubMed...
  39. Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, et al. Retinoic acid receptors (RARs). In: Laudet V, editor. The NC-IUPHAR Compendium on nuclear receptors. The International Union of Basic and Clinical Pharmacology; 2006. p. 128-45.