Regulation of 25-hydroxyvitamin D-1alpha-hydroxylase by epidermal growth factor in prostate cells.
Regulation of 25-hydroxyvitamin D-1alpha-hydroxylase by epidermal growth factor in prostate cells.
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前列腺细胞中表皮生长因子对 25-羟基维生素 D-1α-羟化酶的调节。
DOI：
10.1016/j.jsbmb.2004.03.091
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Chen,TaiC
中科院分区：
文献类型：
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作者：
Wang,Lilin;Flanagan,JohnN;Whitlatch,LymanW;Jamieson,DanielP;Holick,MichaelF;Chen,TaiC
越来越多的数据表明，1α，25-二羟基维生素D （1α,25(OH)2D）的局部产生可能以自分泌方式在前列腺细胞中提供重要的细胞生长调节机制。之前，我们证实了1α- oase酶活性在非癌细胞（PZHPV-7）和癌细胞（PC-3, DU145, LNCaP）中的差异表达，这似乎与1α- oase m-RNA合成及其启动子活性相关。由于EGF通过自分泌和旁分泌环调节前列腺细胞的增殖，而1α，25(OH)2D抑制前列腺细胞的增殖，我们研究了EGF是否也调节前列腺细胞中1α- oase的表达。我们发现EGF上调PZ-HPV-7的1α- oase启动子活性和酶活性，而1α，25(OH) 2d3抑制EGF依赖性的1α- oase酶活性上调。此外，EGF刺激的启动子活性被MAPKK抑制剂PD98059抑制了70%，这表明MAPK途径可能是EGF调节前列腺1α- oase增加1α，25(OH)2D合成的一个途径，作为细胞生长的反馈调节剂。由于EGF对LNCaP细胞中的1α- oase启动子活性没有影响，我们提出，在癌细胞中，EGF刺激1α，25(OH)2D合成的能力可能被取消或减弱。
Accumulating data suggest that local production of 1α,25-dihydroxyvitamin D (1α,25(OH)2D) could provide an important cell growth regulatory mechanism in an autocrine fashion in prostate cells. Previously, we demonstrated a differential expression of 1α-OHase enzymatic activity among noncancerous (PZHPV-7) and cancer cells (PC-3, DU145, LNCaP), which appears to correlate with 1α-OHase m-RNA synthesis and its promoter activities. Since it is well-established that EGF regulates the proliferation of prostate cells via autocrine and paracrine loops and 1α,25(OH)2D inhibites prostate cell proliferation, we investigated if EGF also regulated 1α-OHase expression in prostate cells. We found that EGF upregulated 1α-OHase promoter activity and enzyme activity in PZ-HPV-7 and that 1α,25(OH)2D3inhibited EGF-dependent up-regulation of 1α-OHase enzymatic activity. Moreover, the EGF-stimulated promoter activity was inhibited 70% by the MAPKK inhibitor, PD98059, suggesting that the MAPK pathway may be one pathway involved in the regulation of prostatic 1α-OHase by EGF to increase1α,25(OH)2D synthesis as a feedback regulator of cell growth. Because EGF has no effect on 1α-OHase promoter activity in LNCaP cells, we propose that the ability of EGF to stimulate 1α,25(OH)2D synthesis may be abolished or diminished in cancer cells.