期刊论文详细信息
Breast Cancer Research
DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-α, ER-β and androgen receptor status
Maria I Arenas2  Ricardo Paniagua2  Antonio Ruíz1  Benito Fraile2  Juan M Alfaro2  Isabel Conde2 
[1] Department of Pathology, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain;Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain
关键词: estrogen receptor-β;    estrogen receptor-α;    DAX-1;    breast cancer;    androgen receptor;   
 received in 2003-11-05, accepted in 2004-01-22,  发布年份 2004
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【 摘 要 】

Background

So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-α and ER-β, and the androgen receptor (AR).

Methods

In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas.

Results

In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status.

Conclusion

DAX-1 might modify the AR and ER-β intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies.

【 授权许可】

   
2004 Conde et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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【 参考文献 】
  • [1]Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F: ERβ inhibits proliferation and invasion of breast cancer cells. Endocrinology 2001, 142:4120-4130.
  • [2]Anderson E, Clarke RB, Howell A: Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia 1998, 3:3-5.
  • [3]Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Wärri A, Weihua Z, Van Noorden S, Wahlstrom T, Coombes RC, Warner M, Gustafsson JA: Estrogen receptor beta in breast cancer. Endocrine-Related Cancer 2002, 9:1-13.
  • [4]Burak WE Jr, Quinn AL, Farrar WB, Brueggeneier RW: Androgens influence estrogen-induced responses in human breast carcinoma cells through cytochrome P450 aromatase. Breast Cancer Res Treat 1997, 44:57-64.
  • [5]McKenna NJ, Lanz RB, O'Malley BW: Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999, 20:321-344.
  • [6]Curtis SW, Washburn T, Sewall C, DiAugustine R, Lindzey J, Couse JF, Korach KS: Physiological coupling of growth factor and steroid receptor signalling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proc Natl Acad Sci USA 1996, 93:12626-12630.
  • [7]Uht RM, Anderson CM, Webb P, Kushner PJ: Transcriptional activities of estrogen and glucocorticoid receptors are functionally integrated at the AP-1 response element. Endocrinology 1997, 138:2900-2908.
  • [8]Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC: Nongenotropic, sex-nonspecific signalling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 2001, 104:719-730.
  • [9]Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS: Tissue distribution and quantitative analysis of estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta) messenger ribonucleic acid in the wild-type and ER alpha-knockout mouse. Endocrinology 1997, 138:4613-4621.
  • [10]McGuire WL: Endocrine therapy of breast cancer. Annu Rev Med 1975, 26:353-363.
  • [11]MacGregor JI, Jordan VC: Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 1998, 50:151-196.
  • [12]Roger P, Sahla ME, Makela S, Gustafsson JA, Baldet P, Rochefort H: Decreased expression of estrogen receptor β protein in proliferative preinvasive mammary tumours. Cancer Res 2001, 61:2537-2541.
  • [13]Jarvinen TA, Pelto-Huikko M, Holli K, Isola J: Estrogen receptor beta is coexpressed with ER alpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am J Pathol 2000, 156:29-35.
  • [14]Speirs V, Kerin MJ: Prognostic significance of oestrogen receptor beta in breast cancer. Br J Surg 2000, 87:405-409.
  • [15]Speirs V: Oestrogen receptor beta in breast cancer: good, bad or still too early to tell? J Pathol 2002, 197:143-147.
  • [16]Shan L, Yang Q, Nakamura M, Nakamura Y, Mori I, Sakurai T, Kakudo K: Active allele loss of the androgen receptor gene contributes to loss of androgen receptor expression in female breast cancers. Biochem Biophys Res Commun 2000, 275:488-492.
  • [17]Wilson CM, McPhaul MJ: A and B forms of the androgen receptor are expressed in a variety of human tissues. Mol Cell Endocrinol 1996, 120:51-57.
  • [18]Brys M, Wojcik M, Romanowicz-Makowska H, Krajewska WM: Androgen receptor status in female breast cancer: RT-PCR and Western blot studies. J Cancer Res Clin Oncol 2002, 128:85-90.
  • [19]Ikeda Y, Swain A, Weber TJ, Hentges KE, Zanaria E, Lalli E, Tamai KT, Sassone-Corsi P, Lovell-Badge R, Camerino G, Parker KL: Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development. Mol Endocrinol 1996, 10:1261-1272.
  • [20]Lalli E, Sassone-Corsi P: DAX-1 an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation. Mol Endocrinol 2003, 17:1445-1453.
  • [21]Holter E, Kotaja N, Mäkela S, Strauss L, Kietz S, Jänne OA, Gustafsson JA, Palvimo J, Treuter E: Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Mol Endocrinol 2002, 16:515-528.
  • [22]UICC: TNM Classification of Malignant Tumour. Geneva: International Union Against Cancer; 1968.
  • [23]Norton A, Jordan S, Yeomans P: Brief high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed specimens. J Pathol 1994, 173:371-379.
  • [24]Hsu SM, Soban E: Colour modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem 1982, 30:1079-1082.
  • [25]Shaw JA, Udokang K, Mosquera JM, Chauhan H, Jones JL, Walker RA: Oestrogen receptors alpha and beta differ in normal human breast and breast carcinomas. J Pathol 2002, 198:450-457.
  • [26]Shoker BS, Jarvis C, Clarke RB, Anderson E, Hewlett J, Davies MP, Sibson DR, Sloane JP: Estrogen receptor-positive proliferating cells in the normal and precancerous breast. Am J Pathol 1999, 155:1811-1815.
  • [27]Yamashita S: Localization and functions of steroid hormone receptors. Histol Histopathol 1998, 13:255-270.
  • [28]Bjornstrom L, Sjoberg M: Signal transducers and activators of transcription as downstream targets of nongenomic estrogen receptor actions. Mol Endocrinol 2002, 16:2202-2214.
  • [29]Mann S, Laucirica R, Carlson N, Younes PS, Ali N, Younes A, Li Y, Younes M: Estrogen receptor beta expression in invasive breast cancer. Human Pathol 2001, 32:113-118.
  • [30]Dotzlaw H, Leygue E, Watson PH, Murphy LC: Expression of estrogen receptor-β in human breast tumours. J Clin Endocrinol Metab 1997, 82:2371-2374.
  • [31]Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997, 138:863-870.
  • [32]Hall JM, McDonnell DP: The estrogen receptor beta-isoform (ER beta) of the human estrogen receptor modulates ER alpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 1999, 140:5566-5578.
  • [33]Simpson ER: Aromatization of androgens in women: current concepts and findings. Fertil Steril 2002, 77:6-10.
  • [34]Pasqualini JR: Role of androgens in breast cancer. J Steroid Biochem Mol Biol 1993, 45:167-172.
  • [35]Isola JJ: Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. J Pathol 1993, 170:31-35.
  • [36]Jenster G, Van der Dorput JAGM, Van Vroonhoven C, van der Kwast TH, Trapman J, Brinkmann AO: Domains of the human androgen receptor involved in steroid binding, transcriptional activation and nuclear binding. Mol Endocrinol 1991, 5:1390-1404.
  • [37]Zhang H, Thomsen JS, Johansson L, Gustafsson JA, Treuter E: DAX-1 functions as an LXXLL-containing corepressor for activated estrogen receptors. J Biol Chem 2000, 275:39855-39859.
  • [38]Horvath LG, Henshall SM, Lee CS, Head DR, Quinn DI, Makela S, Delprado W, Golovsky D, Brenner PC, O'Neill G, Kooner R, Stricker PD, Grygiel JJ, Gustafsson JA, Sutherland RL: Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res 2001, 61:5331-5335.
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