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Protein kinase c pathway is involved in regulating the secretion of prostatic acid phosphatase in human prostate cancer cells.

机译:蛋白激酶C途径参与调节人前列腺癌细胞中前列腺酸磷酸酶的分泌。

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The stimulated secretion of prostatic acid phosphatase (PAcP) has been known to be a hallmark of androgen action on human prostate epithelial cells for the last five decades. The molecular mechanism of androgen action on PAcP secretion, however, has remained mostly unknown. We investigated the molecular mechanism that promotes PAcP secretion in LNCaP human prostate carcinoma cells which express PAcP and are androgen-responsive. Treatment with 12-o-tetradecanoyl phorbol-13-acetate (TPA), a protein kinase C (PKC) activator, resulted in an increased secretion of PAcP in a dose- and time-dependent fashion. 4Alpha-phorbol, a biologically inactive isomer of TPA, had no effect. This TPA stimulation of PAcP secretion was observed 2 h after exposure, while TPA did not have a significant effect on the mRNA level even with a 6 h treatment. A23187 calcium ionophore, known to mobilize cellular calcium which is a co-factor of PKC, also activated PAcP secretion. This TPA stimulation of PAcP secretion was more potent than the conventional stimulating agent 5alpha-dihydrotestosterone (DHT) at the same concentration of 50 nM. Furthermore, the action of TPA and DHT on PAcP secretion was blocked by five different PKC inhibitors. Results also showed that DHT, as well as TPA, could rapidly modulate PKC activity. Therefore, PKC can regulate PAcP secretion, and may also be involved in DHT action on PAcP secretion.
机译:在过去的五十年中,已知刺激的前列腺酸磷酸酶(PAcP)分泌是雄激素作用于人前列腺上皮细胞的标志。然而,雄激素对PAcP分泌的作用的分子机制仍然未知。我们调查了表达PAcP和雄激素反应的LNCaP人前列腺癌细胞中促进PAcP分泌的分子机制。用蛋白激酶C(PKC)激活剂12-邻十四烷酰基佛波醇13-乙酸酯(TPA)处理,导致PAcP分泌增加,且呈剂量和时间依赖性。 4α-佛波醇是TPA的一种生物惰性异构体,没有作用。暴露后2 h观察到TPA刺激PAcP分泌,而即使经过6 h处理,TPA对mRNA水平也没有显着影响。已知会动员作为PKC辅助因子的细胞钙的A23187钙离子载体也激活了PAcP分泌。在浓度为50 nM的情况下,这种TPA刺激PAcP分泌的作用比常规刺激剂5α-二氢睾丸激素(DHT)更为有效。此外,TPA和DHT对PAcP分泌的作用被五种不同的PKC抑制剂阻断。结果还表明,DHT和TPA可以快速调节PKC活性。因此,PKC可以调节PAcP的分泌,也可能参与DHT对PAcP分泌的作用。

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