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蛋白激酶CK2信号的核基质靶向作为前列腺癌细胞雄激素或生长因子刺激的常见下游反应。

Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells.

作者信息

Guo C, Yu S, Davis A T, Ahmed K

机构信息

Department of Laboratory Medicine and Pathology, University of Minnesota, and the Department of Veterans Affairs Medical Center, Minneapolis 55417, USA.

出版信息

Cancer Res. 1999 Mar 1;59(5):1146-51.

PMID:10070976
Abstract

Protein kinase CK2, a messenger-independent serine/threonine kinase, has been implicated in cell growth. Androgenic stimulus in rat prostate modulates its association with nuclear matrix (NM) and chromatin. Because the growth of human prostate carcinoma cells is influenced by androgens and/or growth factors, we determined the nature of CK2 signaling in the NM in response to androgen and growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3 cells were cultured in media to regulate their growth in the presence of 5alpha-dihydrotestosterone (5alpha-DHT) or growth factors (epidermal growth factor, keratinocyte growth factor, and transforming growth factor alpha). The activity of CK2 was measured in the cytosolic and NM fractions isolated from these cells after treatment with growth stimuli. The changes in CK2 in various fractions were also confirmed by immunoblotting with a specific antibody. LNCaP cells responded to both 5alpha-DHT and growth factors for growth. The presence of these agents in the culture medium evoked a translocation of CK2 to the NM from the cytosol. The PC-3 cells did not respond to 5alpha-DHT for growth but did respond to growth factors. Under these conditions, there was also a translocation of CK2 to the NM concomitant with a decrease in the cytosolic fraction. These results suggest that CK2 translocation to the NM occurs in response to various growth stimuli in cells in culture. Thus, CK2 is a common downstream signal transducer in response to diverse growth stimuli that may relate to the pathobiology of prostate cancer cells.

摘要

蛋白激酶CK2是一种不依赖信使的丝氨酸/苏氨酸激酶,与细胞生长有关。大鼠前列腺中的雄激素刺激可调节其与核基质(NM)和染色质的结合。由于人前列腺癌细胞的生长受雄激素和/或生长因子的影响,我们确定了NM中CK2信号在雄激素和生长因子刺激下的性质。将雄激素敏感的LNCaP细胞和雄激素不敏感的PC-3细胞培养在含有5α-二氢睾酮(5α-DHT)或生长因子(表皮生长因子、角质形成细胞生长因子和转化生长因子α)的培养基中,以调节它们的生长。在用生长刺激剂处理这些细胞后,测定胞质和NM组分中CK2的活性。用特异性抗体进行免疫印迹也证实了各组分中CK2的变化。LNCaP细胞对5α-DHT和生长因子的生长刺激均有反应。培养基中这些因子的存在引起CK2从胞质向NM的转位。PC-3细胞对5α-DHT的生长刺激无反应,但对生长因子有反应。在这些条件下,也有CK2向NM的转位,同时胞质组分减少。这些结果表明,在培养的细胞中,CK2向NM的转位是对各种生长刺激的反应。因此,CK2是对多种生长刺激的常见下游信号转导分子,这可能与前列腺癌细胞的病理生物学有关。

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Nuclear matrix targeting of the protein kinase CK2 signal as a common downstream response to androgen or growth factor stimulation of prostate cancer cells.蛋白激酶CK2信号的核基质靶向作为前列腺癌细胞雄激素或生长因子刺激的常见下游反应。
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