Reduced expression and homozygous deletion of annexin A10 in gastric carcinoma.
Annexins (ANXs) are a family of calcium and phospholipid binding proteins that have been implicated in diverse important biological and physiological process. ANX A10 (ANXA10) is a member of this family, though little is known about its functions. In the present study, array based comparative genomic hybridization (CGH) was used to screen DNA copy number change in gastric cancer cell lines and the results obtained were compared with oligonucleotide microarray data. DNA loss of the ANXA10 locus in chromosome 4q33 was found in several gastric cancer cell lines by array based CGH and these cell lines showed decreased ANXA10 expression by oligonucleotide microarray analysis. Functional analysis using siRNA and full-length cDNA transfection in gastric cancer cell lines demonstrated that ANXA10 regulates gastric cancer cell proliferation. Of the 585 primary gastric carcinoma tissues examined, ANXA10 expression at the protein level was found to be reduced in 289 (49.4%) cases. Quantitative real-time PCR analysis validated loss of DNA at the ANXA10 locus in gastric carcinomas with reduced ANXA10 expression. By univariate survival analysis, lack of ANXA10 expression was associated with poor survival (p = 0.016). These results suggest that ANXA10 inactivation by chromosomal deletion may play a role during gastric cancer progression.
Kim
Jin
J
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Kim
Min A
MA
Jee
Chang Do
CD
Jung
Eun Ji
EJ
Kim
Woo Ho
WH
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D017302:Annexins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003114:Colony-Forming Units Assay; D055028:Comparative Genomic Hybridization; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007668:Kidney / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D014945:Wound Healing
C121387:ANXA10 protein, human; D017302:Annexins; D012333:RNA, Messenger; D034741:RNA, Small Interfering