Impact of testosterone on the expression of organic anion transporting polypeptides (OATP-1A2, OATP-2B1, OATP-3A1) in malignant and non-malignant human breast cells in vitro
| Autor: | Anne Reichenbach, Petra Stute, Martin Götte, Thomas Szuwart, Ludwig Kiesel |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Organic Anion Transporters Obstetrics and Gynecology Estrogen receptor Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology In vitro Up-Regulation Blot Endocrinology Downregulation and upregulation Cell culture Hormone receptor Cell Line Tumor Internal medicine Androgens medicine Humans Female Testosterone Breast Estrogen receptor alpha Estrogen receptor beta |
| Zdroj: | Maturitas. 71:376-384 |
| ISSN: | 0378-5122 |
| DOI: | 10.1016/j.maturitas.2011.12.020 |
| Popis: | Objectives Postmenopausal hormone therapy (HT) increases local estrogen formation in breast tissue. The enzymatic substrates depend on transmembrane anion transporting polypeptides (OATPs) to reach intracellular enzymes. The aim of this study was to investigate the effect of testosterone (T) on the expression of OATP-1A2, OATP-2B1, and OATP-3A1 in malignant (MCF-7, BT-474) and non-malignant (HBL-100) breast cells in vitro. Study design Cells were incubated in RPMI 1640 medium containing 5% steroid-depleted fetal calf serum for 3d, and subsequently incubated in the absence or presence of T, anastrozole (A), and T+A (10−6 M) for 24 h at 37 °C. Main outcome measures OATP expression was determined by immunocytochemical staining. Expression intensity was graded as low, moderate, or strong. Hormone receptor (AR, PR, ESR1, ESR2) expression was investigated by qPCR and Western blotting. Rank variance analysis was performed for statistical analysis (p ≤ 0.05). Results OATP-1A2, OATP-2B1, and OATP-3A1 expression was present in all untreated breast cell lines examined, with OATP-1A2 and OATP-3A1 being the predominant ones. There was a trend for a higher baseline expression in untreated HBL-100 and BT-474 in comparison to MCF-7 cells, which was significant for OATP-2B1. T treatment led to decreased OATP-1A2, -2B1, and -3A1 expression in BT-474 and HBL-100 cells, respectively. In contrast, in MCF-7 cells, OATP-2B1 expression was significantly increased. T-induced upregulation of AR and PR protein expression in BT-474 and MCF-7 cells was reduced by A treatment. Conclusions T may constitute a signal for differential regulation of mammary OATP expression. In non-malignant breast cells T seems to have a beneficial effect by reducing the availability of substrates for the intracellular formation of potent estrogens. |
| Databáze: | OpenAIRE |
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