DEGA/AMIGO-2, a leucine-rich repeat family member, differentially expressed in human gastric adenocarcinoma: effects on ploidy, chromosomal stability, cell adhesion/migration and tumorigenicity.
We have discovered DEGA, a novel cDNA differentially expressed in human gastric adenocarcinomas. The DEGA gene product contains a signal peptide, five leucine-rich repeat motifs and a single IgG, and transmembrane domain, suggesting its residence on the plasma membrane. Transfection of 293 cells with a DEGA-GFP fusion construct confirmed its cell surface localization. Although the cytosolic portion of the DEGA gene product does not contain known protein domains, approximately one-fifth of these residues are either a serine or a threonine, suggesting that DEGA may play a role in signal transduction. BLAST searches revealed DEGA to be an exact match to AMIGO-2, a recently identified, but functionally uncharacterized protein related to AMIGO, a leucine-rich repeat containing cell adhesion molecule implicated in axon tract development. In this report, we show that DEGA/AMIGO-2 mRNA is differentially expressed in approximately 45% of tumor versus normal tissue from gastric adenocarcinoma patients. Stable expression of a DEGA/AMIGO-2 antisense construct in the gastric adenocarcinoma cell line, AGS, led to altered morphology, increased ploidy, chromosomal instability, decreased cell adhesion/migration, and a nearly complete abrogation of tumorigenicity in nude mice. These findings suggest a potential etiologic role for DEGA/AMIGO-2 in gastric adenocarcinoma.
Rabenau
Karen E
KE
Department of Molecular and Cellular Biology, ImClone Systems Incorporated, New York, NY 10014, USA.
O'Toole
Jennifer M
JM
Bassi
Rajiv
R
Kotanides
Helen
H
Witte
Larry
L
Ludwig
Dale L
DL
Pereira
Daniel S
DS
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001549:Benzamides / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D043171:Chromosomal Instability; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D007930:Leucine; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000209:etiology; D011003:Ploidies; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D001549:Benzamides; D018076:DNA, Complementary; C057944:N-(2,6-dimethylphenyl)-4-(((diethylamino)acetyl)amino)benzamide; D007930:Leucine