Abstract:
:Cathepsin B (CTSB) is overexpressed in tumors of the lung, prostate, colon, breast, and stomach. However, evidence of primary genomic alterations in the CTSB gene during tumor initiation or progression has been lacking. We have found a novel amplicon at 8p22-23 that results in CTSB overexpression in esophageal adenocarcinoma. Amplified genomic NotI-HinfI fragments were identified by two-dimensional DNA electrophoresis. Two amplified fragments (D4 and D5) were cloned and yielded unique sequences. Using bacterial artificial chromosome clones containing either D4 or D5, fluorescent in situ hybridization defined a single region of amplification involving chromosome bands 8p22-23. We investigated the candidate cancer-related gene CTSB, and potential coamplified genes from this region including farnesyl-diphosphate farnesyltransferase (FDFT1), arylamine N-acetyltransferase (NAT-1), lipoprotein lipase (LPL), and an uncharacterized expressed sequence tag (D8S503). Southern blot analysis of 66 esophageal adenocarcinomas demonstrated only CTSB and FDFT1 were consistently amplified in eight (12.1%) of the tumors. Neither NAT-1 nor LPL were amplified. Northern blot analysis showed overexpression of CTSB and FDFT1 mRNA in all six of the amplified esophageal adenocarcinomas analyzed. CTSB mRNA overexpression also was present in two of six nonamplified tumors analyzed. However, FDFT1 mRNA overexpression without amplification was not observed. Western blot analysis confirmed CTSB protein overexpression in tumor specimens with CTSB mRNA overexpression compared with either normal controls or tumors without mRNA overexpression. Abundant extracellular expression of CTSB protein was found in 29 of 40 (72. 5%) of esophageal adenocarcinoma specimens by using immunohistochemical analysis. The finding of an amplicon at 8p22-23 resulting in CTSB gene amplification and overexpression supports an important role for CTSB in esophageal adenocarcinoma and possibly in other tumors.
journal_name
Proc Natl Acad Sci U S Aauthors
Hughes SJ,Glover TW,Zhu XX,Kuick R,Thoraval D,Orringer MB,Beer DG,Hanash Sdoi
10.1073/pnas.95.21.12410subject
Has Abstractpub_date
1998-10-13 00:00:00pages
12410-5issue
21eissn
0027-8424issn
1091-6490journal_volume
95pub_type
杂志文章abstract::Because many survivors of mass extinctions do not participate in postrecovery diversifications, and therefore fall into a pattern that can be termed "Dead Clade Walking" (DCW), the effects of mass extinctions extend beyond the losses observed during the event itself. Analyses at two taxonomic levels provide a first-or...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.102163299
更新日期:2002-06-11 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1997-04-29 00:00:00
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更新日期:2017-09-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2015-07-28 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1986-12-01 00:00:00
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abstract::We estimated the unliganded opening and closing rate constants of neuromuscular acetylcholine receptor-channels (AChRs) having mutations that increased the gating equilibrium constant. For some mutant combinations, spontaneous openings occurred in clusters. For 25 different constructs, the unliganded gating equilibriu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2009-01-06 00:00:00
abstract::During natural fertilization, mammalian spermatozoa must pass through the zona pellucida before reaching the plasma membrane of the oocyte. It is assumed that this step involves partial lysis of the zona by sperm acrosomal enzymes, but there has been no unequivocal evidence to support this view. Here we present eviden...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2020-02-04 00:00:00
abstract::We present whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125-Mb reference genome sequence released a decade ago. Using a newly developed reference-guided approach, we assembled large contigs from 9 to 42 Gb of Illumina short-read data from the Landsberg erecta (Ler-1), C24,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-06-21 00:00:00