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神经生长因子诱导克隆B亚家族及阿片促黑皮质素原基因在肺癌细胞系中的表达

Expression of nerve growth factor-induced clone B subfamily and pro-opiomelanocortin gene in lung cancer cell lines.

作者信息

Ueda Y, Bandoh S, Fujita J, Sato M, Yamaji Y, Takahara J

机构信息

First Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.

出版信息

Am J Respir Cell Mol Biol. 1999 Jun;20(6):1319-25. doi: 10.1165/ajrcmb.20.6.3577.

Abstract

Nerve growth factor-induced clone B (NGFI-B), Nur-related factor 1, and neuron-derived orphan receptor-1 have structural features of ligand-activated transcriptional regulators and constitute the NGFI-B subfamily within the nuclear receptor superfamily. The NGFI-B subfamily is highly expressed in neuroendocrine organs and regulates the pro-opiomelanocortin (POMC) gene. Small-cell lung cancer (SCLC) is considered to be a neuroendocrine tumor that produces large numbers of polypeptide hormones. In this study we measured the NGFI-B subfamily and POMC messenger RNA (mRNA) levels in various lung-cancer cell lines by means of the quantitative reverse transcription-polymerase chain reaction, and evaluated the correlations between expression of these genes and polypeptide hormone productions. We also examined the effect of antisense oligonucleotide to NGFI-B mRNA on the expression of POMC mRNA. The NGFI-B subfamily and POMC mRNAs were highly expressed in SCLC cell lines. In addition, there were strong correlations between the NGFI-B, POMC genes, and the adrenocorticotropin hormone (ACTH) level. Further, the antisense oligonucleotide significantly suppressed POMC gene expression. We conclude that the NGFI-B subfamily was a significant molecule in SCLC and that the NGFI-B was a positive transcriptional factor for ACTH production.

摘要

神经生长因子诱导克隆B(NGFI-B)、Nur相关因子1和神经元衍生孤儿受体1具有配体激活转录调节因子的结构特征,构成核受体超家族中的NGFI-B亚家族。NGFI-B亚家族在神经内分泌器官中高度表达,并调节阿片促黑素皮质素原(POMC)基因。小细胞肺癌(SCLC)被认为是一种产生大量多肽激素的神经内分泌肿瘤。在本研究中,我们通过定量逆转录-聚合酶链反应测量了各种肺癌细胞系中NGFI-B亚家族和POMC信使核糖核酸(mRNA)水平,并评估了这些基因的表达与多肽激素产生之间的相关性。我们还研究了针对NGFI-B mRNA的反义寡核苷酸对POMC mRNA表达的影响。NGFI-B亚家族和POMC mRNAs在SCLC细胞系中高度表达。此外,NGFI-B、POMC基因与促肾上腺皮质激素(ACTH)水平之间存在强相关性。此外,反义寡核苷酸显著抑制了POMC基因表达。我们得出结论,NGFI-B亚家族是SCLC中的一个重要分子,并且NGFI-B是ACTH产生的正转录因子。

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