Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells
Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells
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DOI：
10.1006/bbrc.1999.0367
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发表时间：
1999-03-24
影响因子：
3.1
通讯作者：
Sone, H
中科院分区：
文献类型：
--
作者：
Jana, NR;Sarkar, S;Sone, H
2，3，7，8-四氯二苯并对二恶英(TCDD)及其相关化合物通过促进配体代谢、改变激素合成、下调受体水平、干扰基因转录等途径调节多种内分泌功能。在本研究中，我们研究了TCDD对雄激素受体(AR)阳性的LNCaP前列腺癌细胞株睾酮信号转导通路的影响，反之亦然。TCDD可诱导这些细胞的CYP1A1 mRMA及相关酶活性，并呈剂量和时间依赖关系。TCDD对正常细胞和睾酮刺激的细胞生长均有抑制作用。10 nM的TCDD作用24小时后，芳香烃受体(AhR)、芳香烃受体核转位蛋白(ARNT)和AR的表达水平无明显变化。睾酮剂量依赖性地抑制TCDD诱导的细胞色素P4501A1mRNA积聚和相关酶活性，而TCDD又剂量依赖性地抑制睾酮依赖性转录活性和睾酮调节的前列腺特异性抗原(PSA)表达。综上所述，这些结果证明了TCDD的抗雄激素功能以及TCDD和睾酮介导的信号转导途径之间的特定配体诱导的双边转录干扰。(C)1999年学术出版社。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds modulate various endocrine functions by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. In the present study, we investigated the effects of TCDD on testosterone signal transduction pathways and vice versa in the androgen receptor (AR) positive LNCaP prostate cancer cell line. TCDD induced CYP1A1 mRMA and related enzyme activity in these cells, with dose and time-dependence. Both normal and testosterone-stimulated cell growth was inhibited by TCDD. The expression levels of the aryl hydrocarbon receptor (AhR), the aryl hydrocarbon receptor nuclear translocator (ARNT), and AR were not affected by exposure to TCDD at a dose of 10 nM for a 24 hr time period. Testosterone treatment dose-dependently inhibited the TCDD-induced CYP1A1 mRNA accumulation and related enzyme activity, Reciprocally, TCDD also dose-dependently inhibited testosterone-dependent transcriptional activity and testosterone-regulated prostate specific antigen (PSA) expression. Taken together, these results demonstrate antiandrogenic functions of TCDD and a specific ligand-induced bilateral transcriptional interference between TCDD and testosterone mediated signal transduction pathways. (C) 1999 Academic Press.