Document Detail

Microsatellite deletions in the c-myb transcriptional attenuator region associated with over-expression in colon tumour cell lines.
MedLine Citation:
PMID:  9135073     Owner:  NLM     Status:  MEDLINE    
In the hemopoietic system c-myb expression is required for proliferation of immature cells and its down-regulation is required for differentiation. In colonic mucosa c-myb expression occurs at levels comparable to immature hemopoietic cells. Inhibition of c-myb expression in colon cell lines, using anti-sense oligonucleotides, indicates that c-myb expression is required for proliferation. However, the mechanism of c-myb regulation during colon cell differentiation has not been explored. Using the LIM1215 and CaCo-2 colon carcinoma cell lines induced to differentiate with sodium butyrate, we demonstrate that c-myb mRNA is down-regulated as an early event in differentiation by a mechanism involving transcriptional attenuation in intron 1. By analogy with procaryotic and eucaryotic genes, transcriptional attenuation probably occurs in a region containing nineteen consecutive thymidine residues. Computer prediction of the secondary structure of the nascent mRNA chain encoded by this region suggests a strong potential for stem-loop formation. Sequence analysis of several colon tumour cell lines reveals mutations in this region that may disrupt transcriptional attenuation and result in the increased c-myb expression observed in colon tumours and tumour cell lines.
M A Thompson; R Flegg; E H Westin; R G Ramsay
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncogene     Volume:  14     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-23     Completed Date:  1997-05-23     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1715-23     Citation Subset:  IM    
Ludwig Institute for Cancer Research, PO Royal Melbourne Hospital, Australia.
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MeSH Terms
Base Sequence
Cell Differentiation
Colonic Neoplasms / genetics,  pathology
Gene Expression Regulation, Neoplastic
Hydrogen Bonding
Microsatellite Repeats
Nucleic Acid Conformation
Polymorphism, Single-Stranded Conformational
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-myb
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Sequence Deletion
Trans-Activators / genetics*
Transcription, Genetic
Tumor Cells, Cultured
Reg. No./Substance:
0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Trans-Activators

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