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胃泌素释放肽基因在人小细胞肺癌中的表达。存在可变剪接产生三种不同mRNA的证据。

Expression of the gastrin-releasing peptide gene in human small cell lung cancer. Evidence for alternative processing resulting in three distinct mRNAs.

作者信息

Sausville E A, Lebacq-Verheyden A M, Spindel E R, Cuttitta F, Gazdar A F, Battey J F

出版信息

J Biol Chem. 1986 Feb 15;261(5):2451-7.

PMID:3003116
Abstract

cDNA clones to human prepro-gastrin-releasing peptide (prepro-GRP) mRNA detect synthesis of prepro-GRP-related transcripts in 4 of 7 small cell lung cancer (SCLC) cell lines and 1 of 2 metastatic SCLC tumors examined. A correlation is noted between prepro-GRP gene expression and the occurrence of bombesin-related immunoreactivity in SCLC cell lines. Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a putative GRP-associated peptide in the pro-GRP precursor. The subcellular distribution of prepro-GRP-related RNAs and structure of SCLC-derived prepro-GRP cDNA clones suggest that all three types of transcript could function as mRNAs, although there are differences in the prevalence of the different RNA types in different cellular compartments. Comparison of the sequence of cDNA clones with the sequence of a genomic prepro-GRP clone reveals that the three forms of prepro-GRP mRNA arise from a single primary transcript which undergoes alternative processing from two splice donor sites to two splice acceptor sites. The predicted amino acid sequence of the translated products of the three mRNAs are quite distinct, leading to predicted pro-GRP molecules of differing structure.

摘要

人胃泌素释放肽原(prepro - GRP)mRNA的cDNA克隆检测到,在检测的7个小细胞肺癌(SCLC)细胞系中的4个以及2个转移性SCLC肿瘤中的1个中,存在prepro - GRP相关转录物的合成。在SCLC细胞系中,观察到prepro - GRP基因表达与蛙皮素相关免疫反应性的出现之间存在相关性。对SCLC中发现的prepro - GRP转录物结构的研究揭示了三种类型的prepro - GRP mRNA,它们在前体GRP中假定的GRP相关肽的结构上有所不同。prepro - GRP相关RNA的亚细胞分布以及SCLC衍生的prepro - GRP cDNA克隆的结构表明,尽管不同RNA类型在不同细胞区室中的丰度存在差异,但所有三种类型的转录物都可能作为mRNA发挥作用。将cDNA克隆的序列与基因组prepro - GRP克隆的序列进行比较,发现三种形式的prepro - GRP mRNA源自单个初级转录物,该转录物经历了从两个剪接供体位点到两个剪接受体位点的可变加工。三种mRNA翻译产物的预测氨基酸序列截然不同,导致预测的pro - GRP分子结构不同。

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