Abstract
Purpose
Estrogen receptor β (ERβ) is the second identified receptor mediating the effects of estrogen on target tissues. The role of ERβ in cancer pathobiology is largely unknown, because specific antibodies have not been available until recently. Initial studies have shown that ERβ expression declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen receptor α (ERα) and a pure antagonist of ERβ, has moderate beneficial effects in human astrocytic neoplasms. However, most published studies agree that glial tumors do not express ERα. The purpose of this study was to explore the expression of ERβ in astrocytic neoplasms.
Methods
ERβ expression was monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade I–IV) and in adjacent non-neoplastic brain tissue.
Results
Moderate or strong nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low-grade astrocytomas, whereas the majority of high-grade tumors were immunonegative or displayed weak immunoreactivity. The progressive decline in ERβ expression paralleled the increase in tumor grade.
Conclusions
In as much as ERβ is possibly the only ER expressed in astrocytes, its decreased expression may play an important role in astrocytic tumor initiation and in the potential response of glial neoplasms to tamoxifen.
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References
Assimakopoulou M, Sotiropoulou-Bonikou G, Maraziotis T, Varakis J (1998) Does sex steroid receptor status have any prognostic or predictive significance in brain astrocytic tumors? Clin Neuropathol 17:27–34
Carroll RS, Zhang J, Dashnr K, Sar M, Black PM (1995) Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:496–503
Chaidarun SS, Swearingen B, Alexander JM (1998) Differential expression of estrogen receptor beta (ER beta) in human pituitary tumors: functional interactions with ER alpha and a tumor-specific splice variant. J Clin Endocrinol Metab 83:3308–3315
Chamberlain MC, Kormanik PA (1999) Salvage chemotherapy with tamoxifen for recurrent anaplastic astrocytomas. Arch Neurol 56:703–708
Chang WY, Prins GS (1999) Estrogen receptor-β: implications for the prostate gland. Prostate 40:115–124
Cheng Y, Pang JC, Ng HK, Ding M, Zhang SF, Zheng J, Liu DG, Poon WS (2000) Pilocytic astrocytomas do not show most of the genetic changes commonly seen in diffuse astrocytomas. Histopathol 37:437–444
Couldwell WT, Hinton DR, He S, Chen TC, Sebat I, Weiss MH, Law RE (1994) Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines. FEBS Lett 345:43–46
Da Rocha AB, Mans DR, Bernard EA, Ruschel C, Logallo AF, Wetmore LA, Leyva A, Schwartsmann G (1999) Tamoxifen inhibits particulate-associated protein kinase C activity, and sensitises cultured human glioblastoma cells not to etoposide but to gamma-radiation and BCNU. Eur J Cancer 35:833–839
Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P (1986) Human estrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature 320:134–139
Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J (1986) Sequence and expression of human estrogen complementary DNA. Science 231:1150–1154
Hall JM, Couse JF, Corah KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872
Hofer S, Herrmann R (2001) Chemotherapy for malignant brain tumors of astrocytic and oligodendroglial lineage. J Cancer Res Clin Oncol 127:91–95
Hu J, Pang JC, Tong CY, Lau B, Yin XL, Poon WS, Jiang CC, Zhou LF, Ng HK (2002) High resolution genome-wide allelotype analysis identifies loss of chromosome 14q as a recurrent genetic alteration in astrocytic tumors. Br J Cancer 87:218–224
Iwasaki K, Toms SA, Barnett GH, Estes ML, Gupta MK, Barna BP (1995) Inhibitory effects of tamoxifen and tumor necrosis factor alpha on human glioblastoma cells. Cancer Immunol Immunother 40:228–234
Khalid H, Yaunaga A, Kishikawa M, Shibata S (1995) Immunohistochemical expression of the estrogen receptor-related antigen (ER-D5) in human intracranial tumors. Cancer 75:2571–2580
Kostantinopoulos PA, Kominea A, Vandoros G, Sykiotis GP, Andrikopoulos P, Varakis J, Sotiropoulou-Bonikou G, Papavassiliou AG (2003) Oestrogen receptor beta (ERβ) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumors dedifferentiation. Eur J Cancer 39:1251–12458
Kruijver FP, Balesar R, Espila AM, Unmehopa UA, Swaab DF (2002) Estrogen receptor-alpha distribution in human hypothalamus in relation to sex and endocrine status. J Comp Neurol 454:115–139
Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Aci 93:5925–5990
Louis DN, Holland EC, Cairncross JG (2001) Glioma classification: a molecular reappraisal. Am J Pathol 159:779–786
Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P (1995) The nuclear receptor supefamily: the second decade. Cell 83:835–839
Moore JT, McKee DD, Sletz-Kesler K, Moore LB, Jones SA, Horne SA, Su JL, Kliener SA, Lehmann JM, Willson TM (1998) Cloning and characterization of human estrogen receptor β isoforms. Biochem Biophys Res Commun 247:75–78
Mosselman S, Polman J, Dijkema R (1996) ER-β: identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49–53
Pettersson K, Gustafsson JA (2000) Estrogen receptor beta acts as a dominant regulator of estrogen signalling. Oncogene 19:4970–4978
Pettersson K, Gustafsson JA (2001) Role of estrogen receptor beta in estrogen action. Annu Rev Physiol 63:165–192
Puchner MJA, Giese A, Zapf S, Grebe M, Westphal M (2001) Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in vivo results. Acta Neurochir (Wien) 143:563–573
Pujol P, Rey JM, Nirde P, Roger P, Gastaldi M, Laffargue F, Rochefort H, Mandelonde T (1998) Differential expression of estrogen receptor-α and –β messanger RNAs as a potential marker of ovarian carcinogenesis. Cancer Res 58:5367–5373
Roberts P, Chumas PD, Picton S, Bridges L, Livingstone JH, Sheridan E (2001) A review of the cytogenetics of 58 pediatric brain tumors. Cancer Genet Cytogenet 131:1-12
Savaskan E, Olivieri G, Meirer F, Ravid R, Muller-Spahn F (2001) Hippocampal estrogen beta-receptor immunoreactivity is increased in Alzheimer’s disease. Brain Res 908:113–119
Shiraishi T, Tabuchi K (2003) Genetic alterations of human brain tumors as molecular prognostic factors. Neuropathology 23:95–108
Speirs V (2002) Oestrogen receptor β in breast cancer: good, bad or still too early to tell? J Pathol 197:143–147
Uhlmann K, Rohde K, Zeller C, Szymes J, Vogel S, Marczinek K, Thiel G, Nurnberg P, Laird PW (2003) Distinct methylation profiles of glioma subtypes. Int J Cancer 106:52–59
Vaquero J, Marcos ML, Martinez R, Bravo G (1983) Estrogen and progesterone-receptor proteins in intracranial tumors. Surg Neurol 19:11–13
Weiss WA (2000) Genetics of brain tumors. Curr Opin Pediatr 12:543–548
Xu S, Zhu X, Zhang S, Yin S, Zhou L, Chen C, Gu J (2001) Over-expression of 1,4-galactosyltransferase I, II, and V in human astrocytoma. J Cancer Res Clin Oncol 127:502–506
Zhang W, Couldwell WT, Song H, Takano T, Kin J, Nedergaard M (2000) Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells. Cancer Res 60:5395–5400
Acknowledgements
We thank Dr Evangelia Ntzani for aid in the statistical analysis and A. Christodoulou for excellent technical assistance.
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Batistatou, A., Stefanou, D., Goussia, A. et al. Estrogen receptor beta (ERβ) is expressed in brain astrocytic tumors and declines with dedifferentiation of the neoplasm. J Cancer Res Clin Oncol 130, 405–410 (2004). https://doi.org/10.1007/s00432-004-0548-9
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DOI: https://doi.org/10.1007/s00432-004-0548-9