Novel exons located more than 200 kb downstream of the previously described 3' exon of the K-sam gene for generating activated forms of KGF receptor

Abstract

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.