Abstract
Meningiomas are generally benign central nervous system neoplasms, which frequently express progesterone receptor (PR) and only rarely express the estrogen receptor (ER). For breast cancer, a relation between steroid hormone receptors and proteins involved in the apoptotic process has been described. For meningiomas, the exact relation between PR and these proteins is not known. In this study, ER, PR, bcl-2 and bcl-2-associated × protein (Bax) expression levels were determined in meningioma cytosols. As a reference for our experimental conditions, we also determined these proteins in breast cancer cytosols.
PR and ER were determined with a ligand-binding assay and scatchard-plot analysis. The expression levels of the anti- and pro-apoptotic proteins, bcl-2 and Bax, respectively, were determined by immunoblotting.
In 65% of the meningioma, bcl-2 expression was found in variable amounts. In contrast to breast cancer, a significant negative association between PR and bcl-2 was found (P < 0.01). Bax expression appeared nobreak constitutive, not related to PR, and 2.6 times higher than breast cancer.
As both PR and bcl-2 appear positively associated with prognosis, the negative relationship between bcl-2 and PR found in this study might have some biological and clinical significance.
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Smith DA, Cahill DW: The biology of meningiomas. Neurosurg Clin N Am 5: 201-215, 1994
McDermott MW: Current treatment of meningiomas. Curr Opin Neurol 9: 409-413, 1996
Grunberg SM: Role of antiprogestational therapy for meningiomas. Hum Reprod 9(Suppl 1): 202-207, 1994
Blankenstein MA, Blaauw G, Lamberts SW: Progestin and estrogen receptors in human meningioma. Clin Neuropharmacol 7: 363-367, 1984
Blankenstein MA, Koehorst SG, van der Kallen CJ, Jacobs HM, van Spriel AB, Donker GH, van't Verlaat JW, Blaauw G, Thijssen JH: Oestrogen receptor independent expression of progestin receptors in human meningioma-a review. J Steroid Biochem Mol Biol 53: 361-365, 1995
Fewings PE, Battersby RD, Timperley WR: Long-term follow up of progesterone receptor status in benign meningioma: a prognostic indicator of recurrence? J Neurosurg 92: 401-405, 2000
Hsu DW, Efird JT, Hedley-Whyte ET: Progesterone and estrogen receptors in meningiomas: prognostic considerations. J Neurosurg 86: 113-120, 1997
Zhang GJ, Kimijima I, Tsuchiya A, Abe R: The role of bcl-2 expression in breast carcinomas (Review). Oncol Rep 5: 1211-1216, 1998
Teixeira C, Reed JC, Pratt MA: Estrogen promotes chemotherapeutic drug resistance by a mechanism involving bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Res 55: 3902-3907, 1995
Mosnier JF, Perret AG, Brunon J, Boucheron S: Expression of the bcl-2 oncoprotein in meningiomas. Am J Clin Pathol 106: 652-659, 1996
Hara A, Hirose Y, Yoshimi N, Tanaka T, Mori H: Expression of Bax and bcl-2 proteins, regulators of programmed cell death, in human brain tumors. Neural Res 19: 623-628, 1997
Karamitopoulou E, Perentes E, Tolnay M, Probst A: Prognostic significance of MIB-1, p53, and bcl-2 immunoreactivity in meningiomas. Hum Pathol 29: 140-145, 1998
EORTC: Revision of the standard for assessment of hormone receptors in human breast cancer. Eur J Cancer 16: 1513-1515, 1980
Blankenstein MA, Blaauw G, Lamberts SW, Mulder E: Presence of progesterone receptors and absence of oestrogen receptors in human intracranial meningioma cytosols. Eur J Cancer Clin Oncol 19: 365-370, 1983
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254, 1976
Towbin H, Staehelin T, Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications 1979. Biotechnology 24: 145-149, 1992
Koehorst SG, Spapens ME, Van Der Kallen CJ, van 't Verlaat JW, Blaauw G, Thijssen JH, Blankenstein MA: Progesterone receptor synthesis in human meningiomas: relation to the estrogen-induced proteins pS2 and cathepsin-D and influence of epidermal growth factor, Forskolin and phorbol ester in vitro. Int J Biol Markers 13: 16-23, 1998
Jacobs HM, van Spriel AB, Koehorst SG, Thijssen JH, Blaauw G, Blankenstein MA: The truncated estrogen receptor alpha variant lacking exon 5 is not involved in progesterone receptor expression in meningiomas. J Steroid Biochem Mol Biol 71: 167-172, 1999
Carroll RS, Zhang J, Black PM: Expression of estrogen receptors alpha and beta in human meningiomas. J Neuro-Oncol 42: 109-116, 1999
Kepes JJ: Meningiomas: Biology, Pathology and Differential Diagnosis. Masson Publishing, USA, NY, 1982
Bickerstaff ER, Small JM, Guest IA: The relapsing course of certain meningiomas in relation to pregnancy and menstruation. J Neurol Neurosurg Psychat 21: 89-91, 1958
Markwalder TM, Waelti E, König MP: Endocrine manipulation of meningiomas with medroxyprogesterone acetate. Effect of MPA on receptor status of meningioma cytosols. Surg Neurol 28: 3-9, 1987
Blankenstein MA, Blaauw G, Croughs RJM: Hormone dependency of meningiomas. The Lancet 17: 1381-1381, 1989
Brandis A, Mirzai S, Tatagiba M, Walter GF, Samii M, Ostertag H: Immunohistochemical detection of female sex hormone receptors in meningiomas: correlation with clinical and histological features. Neurosurgery 33: 212-217, 1993
Maier H, Wanschitz J, Sedivy R, Rossler K, Ofner D, Budka H: Proliferation and DNA fragmentation in meningioma subtypes. Neuropathol Appl Neurobiol 23: 496-506, 1997
Ng HK, Chen L: Apoptosis is associated with atypical or malignant change in meningiomas. An in situ labelling and immunohistochemical study. Histopathology 33: 64-70, 1998
Patsouris E, Davaki P, Kapranos N, Davaris P, Papageorgiou K: A study of apoptosis in brain tumors by in situ end-labeling method. Clin Neuropathol 15: 337-341, 1996
Kandouz M, Lombet A, Perrot JY, Jacob D, Carvajal S, Kazem A, Rostene W, Therwath A, Gompel A: Proapoptotic effects of antiestrogens, progestins and androgen in breast cancer cells. J Steroid Biochem Mol Biol 69: 463-471, 1999
Marone M, Scambia G, Mozzetti S, Ferrandina G, Iacovella S, De Pasqua A, Benedetti-Panici P, Mancuso S: Bcl-2, bax, bcl-xl, bcl-xs expression in normal and neoplastic ovarian tissues. Clin Cancer Res 4: 517-524, 1998
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Verheijen, F., Donker, G., Viera, C.S. et al. Progesterone Receptor, Bcl-2 and Bax Expression in Meningiomas. J Neurooncol 56, 35–41 (2002). https://doi.org/10.1023/A:1014404918118
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DOI: https://doi.org/10.1023/A:1014404918118