| Autor: |
Blok, L J, Chang, G T G, Steenbeek-Slotboom, M, Weerden, W M van, Swarts, H G P, Pont, J J H H M De, Steenbrugge, G J van, Brinkmann, A O |
| Předmět: |
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| Zdroj: |
British Journal of Cancer; 9/1/99, Vol. 81 Issue 1, p28, 9p |
| Abstrakt: |
The β1-subunit of Na[SUP+],K[SUP+]-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of androgens. Down-regulation of the β1-subunit was initiated at concentrations between 0.01 nM and 0.03 nM of the synthetic androgen R1881 after relatively long incubation times (> 24 h). Using polyclonal antibodies, the concentration of β1-subunit protein, but not of the α1-subunit protein, was markedly reduced in androgen-dependent human prostate cancer cells (LNCaP-FGC) cultured in the presence of androgens. In line with these observations it was found that the protein expression of total Na[SUP+],K[SUP+]-ATPase in the membrane (measured by [SUP3]H-ouabain binding) was also markedly decreased. The main function of Na[SUP+],K[SUP+]-ATPase is to maintain sodium and potassium homeostasis in animal cells. The resulting electrochemical gradient is facilitative for transport of several compounds over the cell membrane (for example cisplatin, a chemotherapeutic agent experimentally used in the treatment of hormone-refractory prostate cancer). Here we observed that a ouabain-induced decrease of Na[SUP+],K[SUP+]-ATPase activity in LNCaP-FGC cells results in reduced sensitivity of these cells to cisplatin-treatment. Surprisingly, androgen-induced decrease of Na[SUP+],K[SUP+]-ATPase expression, did not result in significant protection against the chemotherapeutic agent. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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