Zusammenfassung
Östrogene spielen eine zentrale Rolle in der Regulation der Physiologie von Brustdrüsengewebe
und Endometrium. Darüber hinaus kommt ihnen eine entscheidende Bedeutung in der Entstehung
und Progression von Malignomen dieser Gewebe zu. Östrogene vermitteln ihre Wirkung
über verschiedene Östrogenrezeptor-Isoformen und -Isotypen. So überwiegt im Brustdrüsengewebe
und im Endometrium die Expression des klassischen ERα, während im Ovar überwiegend
der alternative ERβ exprimiert wird. Diese Übersicht fasst kurz die Struktur, Funktion
und Expression dieser Rezeptoren unter besonderer Berücksichtigung des Endometriumkarzinoms
zusammen. Erste Ergebnisse deuten darauf, dass eine Verschiebung des physiologischen
ERα/ERβ-Verhältnisses in Endometriumkarzinomen mit einer schlechten klinischen Prognose
korreliert. Darüber hinaus wird die klinische Relevanz der differenziellen Östrogenrezeptorexpression
im Hinblick auf eine Antihormontherapie dargestellt.
Summary
Estrogens play a crucial role in the regulation of the physiology of breast tissue
and endometrium. Furthermore, estrogen has been implicated in the initiation and progression
of neoplasms of these tissues. Estrogens mediate their effects through various estrogen
receptor isoforms and isotypes. In breast tissue and in the endometrium the classical
estrogen receptor ERα represents the mainly expressed ER isoform, whereas in the ovary
the alternative estrogen receptor ERβ is predominantly expressed. This review briefly
describes the structure, function and expression of these receptors with special regard
to endometrial cancer. Recent data indicate that alterations of the physiological
ERα/ERβ ratio in endometrial cancer correlates with poor clinical outcome. The potential
clinical relevance of differential ER-isotype expression is also discussed with respect
to an antihormonal therapy.
Schlüsselwörter
Östrogenrezeptor - Endometrium - Karzinom
Key words
Estrogen receptor - Endometrium - Carcinoma
Literatur
- 1
Beato M, Herrlich P, Schutz G.
Steroid hormone receptors: many actors in search of a plot.
Cell.
1995;
83
851-857
- 2
Enmark E, Gustafsson J A.
Oestrogen receptors - an overview.
J Intern Med.
1999;
246
133-138
- 3
Green S, Kumar V, Krust A, Walter P, Chambon P.
Structural and functional domains of the estrogen receptor.
Cold Spring Harb Symp Quant Biol.
1986;
51
751-758
- 4
Green S, Walter P, Greene G, Krust A, Goffin C, Jensen E, Scrace G, Waterfield M,
Chambon P.
Cloning of the human oestrogen receptor cDNA.
J Steroid Biochem.
1986;
24
77-83
- 5
Gustafsson J A.
An update on estrogen receptors.
Semin Perinatol.
2000;
24
66-69
- 6
Hanstein B, Eckner R, DiRenzo J, Halachmi S, Liu H, Searcy B, Kurokawa R, Brown M.
p300 is a component of an estrogen receptor coactivator complex.
Proc Natl Acad Sci USA.
1996;
93
11540-11545
- 7
Hanstein B, Liu H, Yancisin M C, Brown M.
Functional analysis of a novel estrogen receptor-beta isoform.
Mol Endocrinol.
1999;
13
129-137
- 8
Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y,
Nishida E, Kawashima H.
Activation of the estrogen receptor through phosphorylation by mitogen-activated protein
kinase.
Science.
1995;
270
1491-1494
- 9
Kuiper G G, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J A.
Cloning of a novel receptor expressed in rat prostate and ovary.
Proc Natl Acad Sci USA.
1996;
93
5925-5930
- 10
Kuiper G G, Lemmen J G, Carlsson B, Corton J C, Safe S H, van der Saag P T, van der
Burg B, Gustafsson J A.
Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.
Endocrinology.
1998;
139
4252-4263
- 11
Lax S F.
Molekulare Pathogenese des Endometriumkarzinoms.
Zentrabl Gynakol.
2002;
124
10-16
- 12
Mangelsdorf D J, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B,
Kastner P, Mark M, Chambon P.
The nuclear receptor superfamily: the second decade.
Cell.
1995;
83
835-839
- 13
Matsuzaki S, Fukaya T, Suzuki T, Murakami T, Sasano H, Yajima A.
Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout
the menstrual cycle.
Mol Hum Reprod.
1999;
5
559-564
- 14
Murphy L C, Dotzlaw H, Leygue E, Douglas D, Coutts A, Watson P H.
Estrogen receptor variants and mutations.
J Steroid Biochem Mol Biol.
1997;
62
363-372
- 15
Onate S A, Tsai S Y, Tsai M J, O'Malley B W.
Sequence and characterization of a coactivator for the steroid hormone receptor superfamily.
Science.
1995;
270
1354-1357
- 16
Paech K. et all .
Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites
[see comments].
Science.
1997;
277
1508-1510
- 17
Saegusa M, Okayasu I.
Changes in expression of estrogen receptors alpha and beta in relation to progesterone
receptor and pS2 status in normal and malignant endometrium.
Jpn J Cancer Res.
2000;
91
510-518
- 18
Utsunomiya H. et al .
Analysis of estrogen receptor alpha and beta in endometrial carcinomas: correlation
with ER beta and clinicopathologic findings in 45 cases.
Int J Gynecol Pathol.
2000;
19
335-341
- 19
Webb P. et al .
The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different
requirements for receptor transactivation functions.
Mol Endocrinol.
1999;
13
1672-1685
Dr. Bettina Hanstein
Universitäts-Frauenklinik Düsseldorf
Moorenstr. 5
D-40225 Düsseldorf
Phone: +49-2 11-8 11 75 01
Fax: +49-2 11-8 11 81 47
Email: Bettina.Hanstein@uni-duesseldorf.de
