Insulin-Like Growth Factor Binding Protein-3 Is Regulated by Dihydrotestosterone and Stimulates Deoxyribonucleic Acid Synthesis and Cell Proliferation in LNCaP Prostate Carcinoma Cells*
| Autor: | Janet L. Martin, Stacey L. Pattison |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Vitamin medicine.medical_specialty medicine.medical_treatment Biology urologic and male genital diseases Insulin-like growth factor-binding protein chemistry.chemical_compound Endocrinology Internal medicine LNCaP Tumor Cells Cultured medicine Humans Insulin-Like Growth Factor I Vitamin D Dose-Response Relationship Drug DNA synthesis Cell growth Binding protein Growth factor Prostatic Neoplasms Dihydrotestosterone DNA DNA Neoplasm Drug Combinations Insulin-Like Growth Factor Binding Protein 2 Insulin-Like Growth Factor Binding Protein 3 chemistry biology.protein Cell Division hormones hormone substitutes and hormone antagonists Thymidine medicine.drug |
| Zdroj: | Endocrinology. 141:2401-2409 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.141.7.7534 |
| Popis: | We have investigated the production and actions of a growth regulatory protein, insulin-like growth factor binding protein (IGFBP)-3, in the androgen-responsive prostate carcinoma cell line LNCaP. Confluent monolayers of cells secreted approximately 0.7 ng/ml IGFBP-3 over 24 h. Dihydrotestosterone (DHT, 10 nM) and 1,25-dihydroxyvitamin D3 (vitamin D, 10 nM) increased IGFBP-3 in media to 149 +/- 15% and 206 +/- 18% of control, respectively, when added separately, and to 453 +/- 28% of control when used in combination. IGFBP-2, secreted at approximately 25-fold higher concentrations than IGFBP-3, was increased 50% by 10 nM DHT, but there was no effect of vitamin D on IGFBP-2 production in the absence or presence of DHT. Cell-associated IGFBP-3, and immunoreactive IGFBP-3 species of 20 kDa and 30 kDa were also increased in response to vitamin D plus DHT. A combination of vitamin D and DHT increased DNA synthesis in LNCaP cells 3-fold, and this was at least partly mediated by endogenous IGFBP-3 because anti-IGFBP-3 IgG, but not nonimmune serum IgG, reduced the stimulatory effect of vitamin D and DHT from 293 +/- 11.6% to 161 +/- 30.7% of control levels (P0.0001). Basal and DHT plus vitamin D-stimulated thymidine incorporation was significantly increased by 50 ng/ml human plasma-derived purified IGFBP-3. After 4 days treatment with vitamin D plus DHT, or pure IGFBP-3, LNCaP cell numbers were increased relative to control. These results indicate a role for IGFBP-3 in the proliferation of androgen-responsive prostate carcinoma cells. |
| Databáze: | OpenAIRE |
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