Ueda T, Sasaki H, Aoyagi K, Narikiyo M, Tsubosa Y, Kuwahara Y, Sakamoto H, Mafune K, Yoshida T, Makuuchi M, Terada M
Genetics Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104-0045, Japan.
Biochem Biophys Res Commun. 1999 Nov 30;265(3):739-45. doi: 10.1006/bbrc.1999.1735.
The K-sam gene was first identified as an amplified gene in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. We have recently found and reported that the carboxyl-terminal exons of K-sam are frequently deleted in the scirrhous type of gastric cancer. The deletion generates preferential expression of at least six novel K-sam-II mRNAs: K-sam-IIH1, -IIH2 and -IIH3/O4, and K-sam-IIO1, -IIO2, and -IIO3, which encode novel proteins lacking the transformation-inhibitory sequence or activated K-sam proteins. In this study, we investigated expression of the previously described K-sam-IIC1 and -IIC3 mRNAs and the novel six K-sam-II mRNAs in 14 gastric cancer cell lines, 7 breast cancer cell lines, and 20 human normal tissues. All the six novel K-sam-II mRNAs were expressed preferentially in the cell lines derived from the scirrhous type of gastric cancers but not in the 7 breast cancer cell lines and the 20 human normal tissues. We further determined the positional relationship of four exons of H1, O1, O2, and O3 out of the six exons of H1, H2, H3/O4, O1, O2, and O3, and found that these four novel K-sam exons were located more than 200 kb downstream of the previously described carboxyl-terminal exon of the K-sam gene. Expression of K-sam-IIH1, -IIO1, and -IIO2 mRNAs encoding activated K-sam products in the scirrhous type of gastric cancer cell lines HSC39, OCUM2M, HSC59, and HSC60 was not due to the deletion of the C1 exon of K-sam.
K-sam基因最初被鉴定为在低分化型尤其是胃癌硬癌型中扩增的基因。我们最近发现并报道，K-sam的羧基末端外显子在胃癌硬癌型中经常缺失。这种缺失导致至少六种新型K-sam-II mRNA的优先表达：K-sam-IIH1、-IIH2和-IIH3/O4，以及K-sam-IIO1、-IIO2和-IIO3，它们编码缺乏转化抑制序列的新型蛋白质或活化的K-sam蛋白。在本研究中，我们调查了先前描述的K-sam-IIC1和-IIC3 mRNA以及六种新型K-sam-II mRNA在14种胃癌细胞系、7种乳腺癌细胞系和20种人类正常组织中的表达情况。所有六种新型K-sam-II mRNA均优先在源自胃癌硬癌型的细胞系中表达，而不在7种乳腺癌细胞系和20种人类正常组织中表达。我们进一步确定了H1、H2、H3/O4、O1、O2和O3这六个外显子中H1、O1、O2和O3四个外显子的位置关系，发现这四个新型K-sam外显子位于K-sam基因先前描述的羧基末端外显子下游超过200 kb处。在胃癌硬癌型细胞系HSC39、OCUM2M、HSC59和HSC60中，编码活化K-sam产物的K-sam-IIH1、-IIO1和-IIO2 mRNA的表达并非由于K-sam的C1外显子缺失。
