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Epigenetic regulation of retinoic acid receptor β2 gene in the initiation of breast cancer

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Abstract

In order to investigate the methylation status of the retinoic acid receptor beta 2 gene (RAR-β2) in breast carcinoma in relation to gene expression and clinicopathological parameters of patients with breast cancer, expression of RAR-β2 gene and methylation status were analyzed in invasive carcinoma, atypical ductal hyperplasia, fibroadenoma specimens, and normal tissues. Our findings showed that RAR-β2 expression was lower in the breast cancer compared to normal tissue and fibroadenoma. The methylation rate of RAR-β2 in breast cancer and precancerous lesions of breast cancer were higher than that of normal tissues. Hypermethylation may be an initial step in breast carcinogenesis.

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References

  1. Lopez-Otin C, Diamandis EP. Breast and prostate cancer: an analysis of common epidemiological, genetic, and biochemical features. Endocr Rev. 1998;19:365–96.

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.

    Article  PubMed  Google Scholar 

  3. Brtko J. Role of retinoids and their cognate nuclear receptors in breast cancer chemoprevention. Cent Eur J Public Health. 2007;15:3–6.

    PubMed  CAS  Google Scholar 

  4. Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. The molecular basis of retinoids’ use in breast cancer chemoprevention. Cell Oncol. 2007;29:183–4.

    PubMed  CAS  Google Scholar 

  5. Pavan B, Biondi C, Dalpiaz A. Nuclear retinoic acid receptor beta as a tool in chemoprevention trials. Curr Med Chem. 2006;13:3553–63.

    Article  PubMed  CAS  Google Scholar 

  6. Minucci S, Ozato K. Retinoid receptors in transcriptional regulation. Curr Opin Genet Dev. 1996;6:567–74.

    Article  PubMed  CAS  Google Scholar 

  7. de The H, Marchio A, Tiollais P, Dejean A. Differential expression and ligand regulation of the retinoic acid receptor alpha and beta genes. EMBO J. 1989;8:429–33.

    PubMed  Google Scholar 

  8. van der Leede BJ, Folkers GE, Kruyt FA, van der Saag PT. Genomic organization of the human retinoic acid receptor beta 2. Biochem Biophys Res Commun. 1992;188:695–702.

    Article  PubMed  Google Scholar 

  9. Hoffmann B, et al. A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter. Mol Endocrinol. 1990;4:1727–36.

    Article  PubMed  CAS  Google Scholar 

  10. Swisshelm K, et al. Down-regulation of retinoic acid receptor beta in mammary carcinoma cell lines and its up-regulation in senescing normal mammary epithelial cells. Cell Growth Differ. 1994;5:133–41.

    PubMed  CAS  Google Scholar 

  11. Widschwendter M, Daxenbichler G, Dapunt O, Marth C. Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells. Cancer Res. 1995;55:2135–9.

    PubMed  CAS  Google Scholar 

  12. Zhang XK, Liu Y, Lee MO, Pfahl M. A specific defect in the retinoic acid response associated with human lung cancer cell lines. Cancer Res. 1994;54:5663–9.

    PubMed  CAS  Google Scholar 

  13. Xu XC, et al. Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. Cancer Res. 1994;54:3580–7.

    PubMed  CAS  Google Scholar 

  14. Houle B, Rochette-Egly C, Bradley WE. Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells. Proc Natl Acad Sci USA. 1993;90:985–9.

    Article  PubMed  CAS  Google Scholar 

  15. Liu Y, et al. Retinoic acid receptor beta mediates the growth-inhibitory effect of retinoic acid by promoting apoptosis in human breast cancer cells. Mol Cell Biol. 1996;16:1138–49.

    PubMed  CAS  Google Scholar 

  16. Lee X, Si SP, Tsou HC, Peacocke M. Cellular aging and transformation suppression: a role for retinoic acid receptor beta 2. Exp Cell Res. 1995;218:296–304.

    Article  PubMed  CAS  Google Scholar 

  17. Sirchia SM, et al. Endogenous reactivation of the RARbeta2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Res. 2002;62:2455–61.

    PubMed  CAS  Google Scholar 

  18. Widschwendter M, et al. Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer. J Natl Cancer Inst. 2000;92:826–32.

    Article  PubMed  CAS  Google Scholar 

  19. Liu F, et al. Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast. Histopathology. 2009;54:741–50.

    Article  PubMed  Google Scholar 

  20. Veronesi U, et al. Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst. 1999;91:1847–56.

    Article  PubMed  CAS  Google Scholar 

  21. Lotan R, et al. Suppression of retinoic acid receptor-beta in premalignant oral lesions and its up-regulation by isotretinoin. N Engl J Med. 1995;332:1405–10.

    Article  PubMed  CAS  Google Scholar 

  22. Berard J, et al. Lung tumors in mice expressing an antisense RARbeta2 transgene. FASEB J. 1996;10:1091–7.

    PubMed  CAS  Google Scholar 

  23. Sabichi AL, Hendricks DT, Bober MA, Birrer MJ. Retinoic acid receptor beta expression and growth inhibition of gynecologic cancer cells by the synthetic retinoid N-(4-hydroxyphenyl) retinamide. J Natl Cancer Inst. 1998;90:597–605.

    Article  PubMed  CAS  Google Scholar 

  24. Deng G, et al. Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science. 1996;274:2057–9.

    Article  PubMed  CAS  Google Scholar 

  25. Yang Q, et al. Biallelic inactivation of retinoic acid receptor beta2 gene by epigenetic change in breast cancer. Am J Pathol. 2001;158:299–303.

    Article  PubMed  CAS  Google Scholar 

  26. Bix M, Locksley RM. Independent and epigenetic regulation of the interleukin-4 alleles in CD4 + T cells. Science. 1998;281:1352–4.

    Article  PubMed  CAS  Google Scholar 

  27. Hollander GA, et al. Monoallelic expression of the interleukin-2 locus. Science. 1998;279:2118–21.

    Article  PubMed  CAS  Google Scholar 

  28. Hu L, et al. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res. 1991;51:3972–81.

    PubMed  CAS  Google Scholar 

  29. Widschwendter M, et al. Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer. Cancer Res. 1997;57:4158–61.

    PubMed  CAS  Google Scholar 

  30. Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet. 1999;21:163–7.

    Article  PubMed  CAS  Google Scholar 

  31. Cote S, Momparler RL. Activation of the retinoic acid receptor beta gene by 5-aza-2′-deoxycytidine in human DLD-1 colon carcinoma cells. Anticancer Drugs. 1997;8:56–61.

    Article  PubMed  CAS  Google Scholar 

  32. Minna JD, Mangelsdorf DJ. Retinoic acid receptor expression abnormalities in lung cancer: important clues or major obstacles? J Natl Cancer Inst. 1997;89:602–4.

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Breast Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, People’s Republic of China

    Jingyan Sun, Xu Xu, Juntian Liu, Hong Liu & Lin Gu

  2. Department of Breast Pathology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, People’s Republic of China

    Li Fu

Authors
  1. Jingyan Sun
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  2. Xu Xu
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  3. Juntian Liu
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  4. Hong Liu
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  5. Li Fu
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  6. Lin Gu
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Corresponding author

Correspondence to Lin Gu.

Additional information

Jingyan Sun and Xu Xu contributed equally to this paper.

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Sun, J., Xu, X., Liu, J. et al. Epigenetic regulation of retinoic acid receptor β2 gene in the initiation of breast cancer. Med Oncol 28, 1311–1318 (2011). https://doi.org/10.1007/s12032-010-9685-y

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  • DOI: https://doi.org/10.1007/s12032-010-9685-y

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