Markowitz S, Krystal G, Lebacq-Verheyden A M, Way J, Sausville E A, Battey J
National Cancer Institute-Navy Medical Oncology Branch, Bethesda, Maryland 20814.
J Clin Invest. 1988 Sep;82(3):808-15. doi: 10.1172/JCI113683.
The gastrin-releasing peptide (GRP) is a neuropeptide hormone and growth factor produced normally by neural and neuroendocrine cells, as well as by human small-cell lung cancer (SCLC) tumors and derived cell lines. This study compares the structure of the human prepro-GRP gene in four SCLC cell lines that express variable levels of steady-state GRP mRNA. The regulation of GRP gene expression appears to be at the level of primary transcription based on nuclear run on studies. In the two SCLC cell lines expressing GRP we find a single transcription start site for GRP mRNA, and near this site we find four DNase I hypersensitive sites. These hypersensitive sites are absent in the two cell lines that do not express GRP. The presence of DNase hypersensitive sites in the promoter region of the GRP gene is the structural feature that best correlates with transcriptional activation. These four DNase hypersensitive sites are candidates for cis acting regulatory regions, which may be important in determining the level of transcription of the human prepro GRP gene.
胃泌素释放肽（GRP）是一种神经肽激素和生长因子，通常由神经细胞和神经内分泌细胞产生，也可由人小细胞肺癌（SCLC）肿瘤及其衍生细胞系产生。本研究比较了四种稳定状态GRP mRNA表达水平不同的SCLC细胞系中人前胃泌素释放肽原（prepro - GRP）基因的结构。基于细胞核转录分析研究，GRP基因表达的调控似乎发生在初级转录水平。在两个表达GRP的SCLC细胞系中，我们发现GRP mRNA有一个单一的转录起始位点，并且在该位点附近发现了四个脱氧核糖核酸酶I（DNase I）超敏位点。在另外两个不表达GRP的细胞系中不存在这些超敏位点。GRP基因启动子区域存在DNase超敏位点是与转录激活最相关的结构特征。这四个DNase超敏位点是顺式作用调控区域的候选位点，这对于确定人前胃泌素释放肽原基因的转录水平可能很重要。
