Plummer H, Catlett J, Leftwich J, Armstrong B, Carlson P, Huff T, Krystal G
Department of Medicine, Medical College of Virginia, Richmond.
Cancer Res. 1993 Sep 15;53(18):4337-42.
The mRNAs encoding the c-kit protooncogene tyrosine kinase receptor and its ligand, hemopoietic stem cell factor, are coexpressed in the majority of small cell lung cancer cell lines, suggesting that an autocrine growth loop may exist. Functional c-kit protein levels correspond well with mRNA levels in these cells. We have observed that those cell lines which express the c-kit gene also express either the L- and N-myc genes; those cell lines which express the c-myc gene do not express the c-kit gene. We have determined, by analyzing several small lung cancer cell lines transfected with a c-myc expression vector, that heterologous expression of c-myc correlates with a marked down-regulation of c-kit expression. Regulation of c-kit expression by the myc gene family may be partly responsible for the differing biological properties of cell lines and tumors which express N- and L-myc versus those that express c-myc.
编码原癌基因c-kit酪氨酸激酶受体及其配体造血干细胞因子的信使核糖核酸(mRNA)在大多数小细胞肺癌细胞系中共同表达,这表明可能存在自分泌生长环。在这些细胞中,功能性c-kit蛋白水平与mRNA水平高度相符。我们观察到,那些表达c-kit基因的细胞系也表达L-myc和N-myc基因;而那些表达c-myc基因的细胞系则不表达c-kit基因。通过分析几种转染了c-myc表达载体的小肺癌细胞系,我们确定c-myc的异源表达与c-kit表达的显著下调相关。myc基因家族对c-kit表达的调控可能部分解释了表达N-myc和L-myc的细胞系及肿瘤与表达c-myc的细胞系及肿瘤在生物学特性上的差异。