CD44 is a potential target of amplification within the 11p13 amplicon detected in gastric cancer cell lines

Classical cytogenetic approaches have revealed many of the chromosomal aber rations that may occur in gastric cancers (GC), although few alterations of specific genes have been identified so far. Genes that affect progression of this disease need to be identified if clinicians are to achieve optimal management of patients with GC. As the first step toward the cloning of gen e(s) that may be involved in gastric carcinogenesis, we examined 25 GC cell lines for aberrations in DNA copy number to detect chromosomal gains and l osses, as well as gene amplifications, by comparative genomic hybridization (CGH). Our CGH study revealed high-level amplifications in chromosomal reg ions that had been well defined in GC but also in sites that had not, inclu ding 3p24, 5p15, 11p11.2-14, 13q34, 15q26, Xp24, and Xq26-28. The minimal c ommon region at 11p13, within the 11p11.2-14 amplicon, harbors the CD44 gen e. Northern and Western blot analyses showed that an alternatively spliced form of CD44, with variant exons 8-10 (CD44E), was overexpressed in all cel l lines bearing the 11p13 amplicon. However, cell adhesion activity was no greater in these lines than in cell lines without amplifications at the CD4 4 locus, suggesting that the major property of upregulated CD44 in these ca ses might be to transduce signals critically associated with growth and pro liferation of the tumor cells. (C) 2000 Wiley-Liss, Inc.