Document Detail


Identification of candidate liver tumor suppressor genes from human 11p11.2 by transcription mapping of microcell hybrid cell lines.
MedLine Citation:
PMID:  12738998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our previous studies utilized a microcell hybrid (MCH) cell line-based functional model of tumor suppression to localize a liver tumor suppressor to human chromosome 11, map the suppressor locus to a <1-Mb region within human 11p11.2, and identify a number of expressed sequence tags (ESTs) and genes that represent candidate liver tumor suppressor genes. The Human Genome Project has recently positioned a number of additional genes, ESTs, and predicted genes within the human 11p11.2 liver tumor suppressor region. In this study, we analyzed 26 ESTs and genes (known and predicted) that have been localized to human 11p11.2. Four of these ESTs/genes (FLJ23598, FLJ10450, KIAA1580, SYT13) mapped to the minimal tumor suppressor region of human 11p11.2, the smallest region conferring suppression of tumorigenicity in the MCH cell lines. Each of these ESTs/genes were expressed among an index panel of suppressed MCH cell lines (derived from GN6TF rat liver tumor cells), suggesting that these ESTs/genes represent excellent candidates for the human 11p11.2 liver tumor suppressor gene. To verify the candidate status of these sequences, 8 additional MCH cell lines (derived from GN3TG and GP10TA rat liver tumor cells) were analyzed. Three ESTs/genes (FLJ23598, FLJ10450, KIAA1580) proved to be less than ideal candidates, based upon their loss from suppressed MCH cell lines (DNA deletion), and/or their retention and expression in a non-suppressed MCH cell line. In contrast, SYT13 is present in the DNA from all suppressed MCH cell lines (n=10), and is deleted in a non-suppressed MCH cell line. Furthermore, SYT13 mRNA is expressed in 100% of suppressed cell lines, and is not expressed in the non-suppressed MCH cell line or in MCH-derived tumor cell lines (n=6). These results suggest that SYT13 is an excellent candidate for the human 11p11.2 liver tumor suppressor gene based upon its: i) location within the human 11p11.2 liver tumor suppressor region; ii) loss from the DNA of a non-suppressed MCH cell line that lacks the human 11p11.2 liver tumor suppressor region; iii) expression among suppressed MCH cell lines; and iv) lack of expression by MCH-derived tumor cell lines.
Authors:
Jennifer E Jahn; Sharon L Ricketts; William B Coleman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of oncology     Volume:  22     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-09     Completed Date:  2003-08-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1303-10     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, Curriculum in Toxicology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Chromosome Mapping
Chromosomes, Human, Pair 11*
DNA Primers
Expressed Sequence Tags
Gene Expression Regulation
Genes, Tumor Suppressor*
Human Genome Project
Humans
Hybrid Cells / pathology
Proteins / genetics
Sequence Deletion
Transcription, Genetic*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA78343/CA/NCI NIH HHS; T32 ES07017/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Proteins

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