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 aberrations 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 gene(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 losses, as well as gene amplifications, by comparative genomic hybridization (CGH). Our CGH study revealed high-level amplifications in chromosomal regions that had been well defined in GC but also in sites that had not, including 3p24, 5p15, 11p11.2-14, 13q34, 15q26, Xp24, and Xq26-28. The minimal common region at 11p13, within the 11p11.2-14 amplicon, harbors the CD44 gene. Northern and Western blot analyses showed that an alternatively spliced form of CD44, with variant exons 8-10 (CD44E), was overexpressed in all cell lines bearing the 11p13 amplicon. However, cell adhesion activity was no greater in these lines than in cell lines without amplifications at the CD44 locus, suggesting that the major property of upregulated CD44 in these cases might be to transduce signals critically associated with growth and proliferation of the tumor cells.
Fukuda
Y
Y
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Kurihara
N
N
Imoto
I
I
Yasui
K
K
Yoshida
M
M
Yanagihara
K
K
Park
J G
JG
Nakamura
Y
Y
Inazawa
J
J
D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002869:Chromosome Aberrations / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology; D005784:Gene Amplification / Q000235:genetics*; D018628:Gene Dosage; D006651:Histocytochemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D018960:Hyaluronan Receptors