Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas.
Amplification of chromosomal DNA is thought to be one of the mechanisms that activate cancer-related genes in tumors. In a recent study, we identified high copy-number amplification at 11q21-q23 in cell lines derived from esophageal squamous cell carcinomas (ESCs) using comparative genomic hybridization. Because 11q21-q23 amplification has been reported in tumors of various other types as well, gene(s) associated with tumor progression may lie within this chromosomal region. To identify the most likely target(s) for amplification at 11q21-q23, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed ESC cell lines for expression levels of 11 known genes and one uncharacterized transcript present within the 1.8-Mb commonly amplified region. Only cIAP1, a member of the IAP (antiapoptotic) gene family, was consistently overexpressed in cell lines that showed amplification. Additionally, the cIAP1 protein was overexpressed in the primary tumors from which those cell lines had been established. The ESC cell lines with cIAP1 amplification were resistant to apoptosis induced by chemotherapeutic reagents. An increase in cIAP1 copy number was also detected in 4 of 42 (9.5%) primary ESC tumors that were not related to the cell lines examined. Because inhibition of apoptosis seems to be an important feature of carcinogenesis, cIAP1 is likely to be a target for 11q21-23 amplification and may be involved in the progression of ESC, as well as other malignancies.
Imoto
I
I
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical & Dental University, Tokyo 113-8510, Japan.
Yang
Z Q
ZQ
Pimkhaokham
A
A
Tsuda
H
H
Shimada
Y
Y
Imamura
M
M
Ohki
M
M
Inazawa
J
J
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D012333:RNA, Messenger; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases