The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with bicalutamide
| Autor: | Barbara Comuzzi, Kamilla Malinowska, Matthias Fiechtl, Alfred Hobisch, Andreas Fritzer, Zoran Culig, Georg Bartsch, Hannes Steiner |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Bicalutamide medicine.drug_class Urology Blotting Western urologic and male genital diseases Antiandrogen Tosyl Compounds Prostate cancer Internal medicine LNCaP Nitriles medicine Tumor Cells Cultured Humans Anilides Receptor Cell Proliferation Chemistry Prostatic Neoplasms Androgen Antagonists Transfection Androgen medicine.disease Up-Regulation Androgen receptor Endocrinology Oncology Drug Resistance Neoplasm Receptors Androgen Disease Progression medicine.drug Signal Transduction |
| Zdroj: | The Prostate. 66(4) |
| ISSN: | 0270-4137 |
| Popis: | Background Experimental work in various prostate cancer models revealed that the androgen receptor is frequently upregulated and implicated in tumor progression. However, little attention has been paid to the androgen receptor-signaling pathway in the development of therapy resistance in patients who receive chronic treatment with a non-steroidal anti-androgen. Methods We have generated a novel subline, LNCaP-Bic, after prolonged treatment with androgen and bicalutamide in vitro. Proliferation of LNCaP-Bic cells in the absence or presence of androgen, tocopherol succinate, and/or bicalutamide was assessed by cell counting. Androgen receptor expression was determined by Western blot. Luciferase activity was measured in cells transfected with an androgen-responsive reporter. Results In basal conditions, proliferation of LNCaP-Bic cells increased more than threefold over that of control LNCaP cells. Neither synthetic androgen R1881 nor bicalutamide showed any effect on LNCaP-Bic growth in vitro. Androgen receptor expression did not differ between the cell subline generated in the presence of bicalutamide and parental LNCaP cells. The ability of R1881 to induce reporter gene activity in LNCaP-Bic cells was reduced by 56%. Tocopherol succinate caused inhibition of proliferation only in the parental cell line although the androgen receptor and prostate-specific antigen were downregulated by the vitamin E derivative in both parental LNCaP and LNCaP-Bic cells. Conclusions Androgen receptor-mediated signal transaction is not enhanced in cells selected in the presence of bicalutamide. Our data may suggest that a more differentiated approach in targeting the androgen receptor is needed in prostate cancers that become resistant to classic endocrine treatment. © 2005 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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