Top

Published in:

01-04-2011 | Laboratory Investigation - Human/Animal Tissue

Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line

Authors: Hongtao Lv, Chuzhong Li, Songbai Gui, Meizhen Sun, Dan Li, Yazhuo Zhang

Published in: Journal of Neuro-Oncology | Issue 2/2011

Abstract

The relationship between estrogen and pituitary prolactinoma is well documented. The biological effects of estrogen are mainly mediated by estrogen receptor α (ERα). Several lines of evidence demonstrate that growth factors such as pituitary tumor transforming gene (PTTG), basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGFβ1), transforming growth factor β3 (TGFβ3), and transforming growth factor β receptor type II (TGFβRII) play an important role in prolactinoma pathogenesis induced by estrogen, but the relationship between ERα and such growth factors is still unclear. The aims of this study are to investigate the functional role of ERα in proliferation, prolactin (PRL) secretion, and expression of the above-mentioned growth factors in MMQ cells in the absence of estrogen and to discuss the feasibility of using an estrogen receptor antagonist to treat prolactinoma. Fulvestrant, a “pure” antiestrogen without any estrogen-like activity, was used to block expression of ERα in the MMQ cell line. Proliferation and PRL secretion of MMQ cells were measured using CellTiter 96^® AQueous One Solution Cell Proliferation Assay (MTS) and the enzyme-linked immunosorbent assay (ELISA) method. Levels of ERα, PTTG, bFGF, TGFβ1, TGFβ3, and TGFβRII were analyzed by real-time polymerase chain reaction (PCR) and Western blot. Fulvestrant significantly inhibited cell proliferation (up to 60.80%) and PRL secretion (up to 77.95%), and changed expression of TGFβ3 and TGFβRII in the absence of estrogen. In conclusion, ERα plays an important functional role in proliferation and PRL secretion of pituitary prolactinomas and also can change expression of some growth factors even under the condition of no estrogen. Fulvestrant could potentially be an effective therapy for treating such tumors.

Yin P, Arita J (2000) Differential regulation of prolactin release and lactotrope proliferation during pregnancy, lactation and the estrous cycle. Neuroendocrinology 72:72–79PubMedCrossRef

Lloyd RV (1983) Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study. Am J Pathol 113:198–206PubMed

Molitch ME (1999) Management of prolactinomas during pregnancy. J Reprod Med 44(12 Suppl):1121–1126PubMed

Carol W, Lauterbach H, Klinger G, Unger A, Michels W (1988) Prolactin stimulation using the metoclopramide test in females taking oral contraceptives. Zentralbl Gynakol 110:1515–1521 (in German)PubMed

Shy KK, McTiernan AM, Daling JR, Weiss NS (1983) Oral contraceptive use and the occurrence of pituitary prolactinoma. JAMA 249:2204–2207PubMedCrossRef

Elias KA, Weiner RI (1984) Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci U S A 81:4549–4553PubMedCrossRef

Raymond V, Beaulieu M, Labrie F, Boissier J (1978) Potent antidopaminergic activity of estradiol at the pituitary level on prolactin release. Science 200:1173–1175PubMedCrossRef

Sarkar Dk, Hentges ST, De A, Reddy RH (1998) Hormonal control of pituitary prolactin-secreting tumors. Front Biosci 3:d934–d943PubMed

Mosselman S, Polman J, Dijkema R (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49–53PubMedCrossRef

10.

Le Goff P, Montano MM, Schodin DJ, Katzenellenbogen BS (1994) Phosphorylation of the human estrogen receptor. Identification of hormone-regulated sites and examination of their influence on transcriptional activity. J Biol Chem 269:4458–4466PubMed

11.

Aronica SM, Katzenellenbogen BS (1991) Progestrone receptor regulation in uterine cells: stimulation by estrogen, cyclic adenosine 3′,5′-monophosphate, and insulin-like growth factor I and supression by antiestrogens and protein kinase inhibitors. Endocrinology 128:2045–2052PubMedCrossRef

12.

Beck CA, Weigel NL, Edwards DP (1992) Effects of hormone and cellular modulators of protein phosphorylation on transcriptional activity, DNA binding, and phosphorylation of human progesterone receptors. Mol Endocrinol 6:607–620PubMedCrossRef

13.

Sirbasku DA (1978) Estrogen induction of growth factors specific for hormone-responsive mammary, pituitary and kidney tumor cells. Proc Natl Acad Sci U S A 75:3786–3790PubMedCrossRef

14.

Soto AM, Sonnenschein C (1987) Cell proliferation of estrogen-sensitive cells: the case for negative control. Endocr Rev 8:44–52PubMedCrossRef

15.

Judd AM, Login IS, Kovacs K, Ross PC, Spangelo BL, Jarvis WD, MacLeod RM (1988) Characterization of the MMQ cell, a prolactin-secreting clonal cell line that is responsive to dopamine. Endocrinology 123:2341–2350PubMedCrossRef

16.

Wakeling AE, Dukes M, Bowler J (1991) A potent specific pure antiestrogen with clinical potential. Cancer Res 51:3867–3873PubMed

17.

Lykkesfeldt AE, Madsen MW, Briand P (1994) Altered expression of estrogen-regulated genes in a tamoxifen-resistant and ICI 164, 384 and ICI 182, 780 sensitive human breast cancer cell line, MCF-7/TAMR-1. Cancer Res 54:1587–1595PubMed

18.

Gottardis MM, Jiang SY, Jeng MH, Jordan VC (1989) Inhibition of tamoxifen-stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Res 49:4090–4093PubMed

19.

Bross PF, Baird A, Chen G, Jee JM, Lostritto RT, Morse DE, Rosario LA, Williams GM, Yang P, Rahman A, Williams G, Pazdur R (2003) Fulvestrant in postmenopausal women with advanced breast cancer. Clin Cancer Res 9:4309–4317PubMed

20.

Fawell SE, White R, Hoare S, Sydenham M, Page M, Parker MG (1990) Inhibition of estrogen receptor-DNA binding by the “pure” antiestrogen ICI 164, 384 appears to be mediated by impaired receptor dimerization. Proc Natl Acad Sci U S A 87:6883–6887PubMedCrossRef

21.

Ignar-Trowbridge DM, Teng CT, Ross KA, Parker MG, Korach KS, McLachlan JA (1993) Peptide growth factors elicit estrogen receptor-dependent transcriptional activation of an estrogen-responsive element. Mol Endocrinol 7:992–998PubMedCrossRef

22.

Improta-Brears T, Whorton AR, Codazzi F, York JD, Meyer T, McDonnell DP (1999) Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc Natl Acad Sci U S A 96:4686–4691PubMedCrossRef

23.

Cenni B, Picard D (1999) Ligand-independent activation of steroid receptors: new roles for old players. Trends Endocrinol Metab 10:41–46PubMedCrossRef

24.

El-Tanani MK, Green CD (1997) Two separate mechanisms for ligand-independent activation of the estrogen receptor. Mol Endocrinol 11:928–937PubMedCrossRef

25.

Heaney AP, Singson R, McCabe CJ, Nelson V, Nakashima M, Melmed S (2000) Pituitary-tumour transforming gene in colorectal tumors. Lancet 355:712–715CrossRef

26.

Heaney AP, Horwitz GA, Wang Z, Singson R, Melmed S (1999) Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Nat Med 5:1317–1321PubMedCrossRef

27.

Amano O, Yoshitake Y, Nishikawa K, Iseki S (1993) Immunocytochemical localization of basic fibroblast growth factor in the rat pituitary gland. Arch Histol Cytol 56:269–276PubMedCrossRef

28.

Elias KA, Weiner RI (1984) Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci U S A 81:4549–4553PubMedCrossRef

29.

Chaturvedi K, Sarkar DK (2004) Involvement of protein kinase C-dependent mitogen-activated protein kinase p44/42 signaling pathway for cross-talk between estradiol and transforming growth factor-beta3 in increasing basic fibroblast growth factor in folliculostellate cells. Endocrinology 145:706–715PubMedCrossRef

30.

Pastorcic M, De A, Boyadjieva N, Vale W, Sarkar DK (1995) Reduction in the expression and action of transforming growth factor β1 on lactotropes during estrogen-induced tumorigenesis in the anterior pituitary. Cancer Res 55:4892–4898PubMed

31.

Minami S, Sarkar DK (1997) Transforming growth factor-β1 inhibits prolactin secretion and lactotropic cell proliferation in the pituitary of estrogen-treated Fischer 344 rats. Neurochem Int 30:499–506PubMedCrossRef

32.

Hentges S, Boyadjieva N, Sarkar DK (2000) Transforming growth factor-β3 stimulates lactotrope cell growth by increasing basic fibroblast growth factor from folliculo-stellate cells. Endocrinology 141:859–867PubMedCrossRef

33.

Brattain MG, Markowitz SD, Willson JKV (1996) The type II transforming growth factor-βreceptor as a tumor-suppressor gene. Curr Opin Oncol 8:49–53PubMedCrossRef

34.

Sarkar DK, Pastorcic M, De A, Engel M, Moses H, Ghasemzadeh B (1998) Role of transforming growth factor (TGF)-βtype I and TGF-β type II receptors in the TGF-β1-regulated gene expression in pituitary prolactin-secreting lactotropes. Endocrinology 139:3620–3628PubMedCrossRef

Title: Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line
Authors: Hongtao Lv
Chuzhong Li
Songbai Gui
Meizhen Sun
Dan Li
Yazhuo Zhang
Publication date: 01-04-2011
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2011
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-010-0326-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of estrogen receptor antagonist on biological behavior and expression of growth factors in the prolactinoma MMQ cell line

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2011

Central nervous system Hodgkin lymphoma: case report and review of the literature

Kitten-transmitted Bordetella bronchiseptica infection in a patient receiving temozolomide for glioblastoma

Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using perfusion CT: an analysis of perfusion parameters helping further characterize genetic subtypes as well as differentiate from astroglial tumors

Factors associated with preservation of facial nerve function after surgical resection of vestibular schwannoma

Phase II trial of ritonavir/lopinavir in patients with progressive or recurrent high-grade gliomas

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study