Sekido Y, Takahashi T, Ueda R, Takahashi M, Suzuki H, Nishida K, Tsukamoto T, Hida T, Shimokata K, Zsebo K M
Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Cancer Res. 1993 Apr 1;53(7):1709-14.
Accumulating evidence suggests that c-kit and its ligand, stem cell factor (SCF), play an important role in the regulation of at least three lineages of stem cell growth and possibly in leukemogenesis, while only limited data are available that suggest possible involvement of c-kit/SCF in the development of human solid tumors such as lung cancer. We have recently reported that c-kit is aberrantly expressed almost exclusively in small-cell lung cancer (SCLC) among various types of solid tumors. The present study revealed that c-kit protein ectopically expressed in SCLC is indistinguishable from that in leukemia cell lines with megakaryocytic characteristics with respect to amount, molecular size, and autophosphorylation status in response to recombinant human SCF. Furthermore, significant chemotactic response as well as moderate in vitro cell growth was induced in SCLC cell lines by the addition of recombinant human SCF, suggesting that c-kit/SCF may play an important biological role in the development of SCLC. Our extensive search for activating mutations naturally occurring in the c-kit gene revealed an amino acid substitution in the transmembrane domain of an SCLC cell line, although the functional consequences of this variant allele are yet to be determined.
越来越多的证据表明，c-kit及其配体干细胞因子（SCF）在至少三种干细胞生长谱系的调节中发挥重要作用，并且可能参与白血病的发生，而关于c-kit/SCF可能参与人类实体瘤如肺癌发展的相关数据却十分有限。我们最近报道，在各种类型的实体瘤中，c-kit几乎只在小细胞肺癌（SCLC）中异常表达。本研究表明，SCLC中异位表达的c-kit蛋白在数量、分子大小以及对重组人SCF的自磷酸化状态方面，与具有巨核细胞特征的白血病细胞系中的c-kit蛋白并无差异。此外，添加重组人SCF可在SCLC细胞系中诱导出显著的趋化反应以及适度的体外细胞生长，这表明c-kit/SCF可能在SCLC的发展中发挥重要的生物学作用。我们对c-kit基因中自然发生的激活突变进行了广泛搜索，发现一个SCLC细胞系的跨膜结构域存在氨基酸替换，尽管该变异等位基因的功能后果尚待确定。
