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In vivo models for endocrine-dependent breast carcinomas

special considerations of clinical relevance

      Abstract

      Tumours in hormone-regulated organs such as the breast, prostate or ovaries are among the most frequent malignancies. Because of their endocrine-dependent development and growth, they offer a unique opportunity for antihormonal treatment either single or long-term or in combination with radio- or chemotherapy. A prominent example is breast carcinoma, for which the anti-oestrogen tamoxifen has been used successfully for several years. Unfortunately, a substantial number of tumours are intrinsically tamoxifen-resistant, despite oestrogen-receptor positivity, and, eventually, almost all breast carcinomas acquire resistance towards tamoxifen. The recently developed pure anti-oestrogen Faslodex™ and the third-generation aromatase inhibitors (Letrozol™, anastrozole (Arimidex™)) offer the possibility of alternative therapies. Preclinical models are needed, as most of the mechanisms of hormonal tumour dependence and the causes of the appearance of antihormone resistance are not yet fully understood. This review focuses on the development and characterisation of breast cancer xenografts derived directly from surgical resections. With their help, a deeper insight into the mechanisms of hormone regulation and anti-oestrogen resistance can be gained. The xenograft models have already been used in differential gene-expression analysis on DNA microarrays and for the evaluation of approaches to overcoming tamoxifen resistance.

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      References

        • Winograd B
        • Boven E
        • Lobbezzo M.W
        • Pinedo H.M
        Human tumor xenografts in the nude mouse and their value as test models in anticancer drug development (Review).
        In vivo. 1987; 1: 1-14
        • Widmaier R
        • Wildner G.P
        • Papsdorf G
        • Graffi I
        A new infinite cell line, MaTu, of human mammary tumor-cells.
        Archiv für Geschwulstforschung. 1974; 44: 1-10
        • Johnston S.R.D
        Acquired tamoxifen resistance in human breast cancer—potential mechanisms and clinical implications.
        Anticancer Drugs. 1997; 8: 911-930
        • Clark R
        • Leonessa F
        • Welch J.N
        • Skaar T.C
        Cellular and molecular pharmacology of antiestrogen action and resistance.
        Pharmacol. Rev. 2001; 53: 25-71
        • Naundorf H
        • Becker M
        • Lykkesfeldt A.E
        • Elbe B
        • Neumann C
        • Büttner B
        • Fichtner I
        Development and characterization of a tamoxifen-resistant breast carcinoma xenograft.
        Brit. J. Cancer. 2000; 82: 1844-1850
        • Brzozowski A.M
        • Pike A.C.W
        • Dauter Z
        • et al.
        Molecular basis of agonism and antagonism in the oestrogen receptor.
        Nature. 1997; 389: 753-758
        • Maalouf G.J
        • Xu W
        • Smith T.F
        • Mohr S.C
        Homology model for the ligand-binding domain of the human estrogen receptor.
        J. Biomol. Struc. Dyn. 1998; 15: 841-851
        • Montana M.M
        • Muller V
        • Trobaugh A
        • Katzenellenbogen B.S
        The carboxy-terminal F domain of the human estrogen receptor.
        Mol. Endocrinol. 1995; 9: 814-825
        • Tonetti D.A
        • Jordan V.C
        The role of estrogen receptor mutations in tamoxifen-stimulated breast cancer.
        J. Steroid. Biochem. Mol. Biol. 1997; 62: 119-128
        • Yao K
        • Lee E.S
        • Bentrem D.J
        • et al.
        Antitumor action of physiological estradiol on tamoxifen-stimulated breast tumors grown in athymic mice.
        Clin. Cancer Res. 2000; 6: 2028-2036
        • Madsen M.W
        • Reiter B.E
        • Larson S.S
        • Briand P
        • Lykkesfeldt A.E
        Estrogen receptor messenger RNA splice variants are not involved in antiestrogen resistance in sublines of MCF-7 human breast cancer cells.
        Cancer Res. 1997; 57: 585-589
        • Tremblay G.B
        • Giguère V
        Coregulators of estrogen receptor action.
        Crit. Rev. Eukaryotic. Gene Expression. 2002; 12: 1-22
        • Clark R
        • Skaar T.C
        • Bouker K.B
        • Davis N
        • Lee Y.R
        • Welch J.N
        • Leonessa F
        Molecular and pharmacological aspects of antiestrogen resistance.
        J. Steroid Biochem. Mol. Biol. 2001; 76: 71-84
        • Katzenellenbogen B.S
        • Montano M.M
        • Ekena K
        • Herman M.E
        • McInerney E.M
        • William L
        McGuire Memorial Lecture. Antiestrogens.
        Breast Cancer Res. Treat. 1997; 44: 23-38
      1. Becker M, Sommer A, Krätzschmar J, Seidel H, Pohlenz H-D, Fichtner I. Oligonucleotide chip analysis reveals distinctive gene expression patterns in Tam-sensitive and-resistant human mammary carcinoma xenografts. 14th EORTC-NCI-AACR symposium on “Molecular Targets and Cancer Therapeutics”, 19–22 Nov 2002, Frankfurt, Germany.

        • Vickers P.J
        • Dickson R.B
        • Shoemaker R
        • Cowan K.H
        A multidrug-resistant MCF-7 human breast cancer cell line which exhibits cross-resistance to antiestrogens and hormone-independent tumor growth in vivo.
        Mol. Endocrinol. 1988; 2: 886-892
        • Zeisig R
        • Arndt D
        • Stahn R
        • Fichtner I
        Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid.
        Biochim. Biophys. Acta. 1998; 1414: 238-248
        • Naundorf H
        • Fichtner I
        • Elbe B
        • et al.
        Establishment and characteristics of two new human mammary carcinoma lines in nude mice with special reference to the estradiol receptor status and the importance of stroma for in vivo and in vitro growth.
        Breast Cancer Res. Treat. 1994; 32: 187-196
        • Naundorf H
        • Fichtner I
        • Saul G.J
        • Haensch W
        • Büttner B
        Establishment and characteristics of two new human mammary carcinoma lines serially transplantable in nude mice.
        J. Cancer Res. Clin. Oncol. 1993; 119: 652-656
        • Fichtner I
        • Naundorf H
        • Saul G.J
        • Zschiesche W
        • Zeisig R
        Establishment and characterization of human xenotransplanted breast carcinoma lines.
        in: Arnold W Köpf-Maier P Micheel B Immunodeficient Animals: Models for Cancer Research, Vol. 51. Contrib Oncol Basel, Karger1996: 129-133
        • Naundorf H
        • Fichtner I
        • Büttner B
        • Frege J
        Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.
        J. Cancer Res. Clin. Oncol. 1992; 119: 35-40
        • Naundorf H
        • Rewasowa E.C
        • Fichtner I
        • Büttner B
        • Becker M
        • Görlich M
        Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives.
        Breast Cancer Res. Treat. 1992; 23: 87-95