Document Detail


Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines.
MedLine Citation:
PMID:  10234815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Keratin intermediate filaments are formed in epithelial cells in a cell- and tissue-specific manner, but much remains unknown regarding the mechanisms which control the synthesis of these proteins. We examined the effect of the differentiation modulation agent, bromodeoxyuridine (BrdU), on two human keratin-negative (by immunocytochemistry) lung cell lines, DLKP and H82, and showed immunohistochemically that treatment with 10 microM BrdU over 7 days induced K8 and K18 protein synthesis in both lines. Immunoprecipitation and Western blot analyses revealed low levels of K8 and K18 proteins in untreated cell homogenates. These levels increased following treatment with BrdU for 7 days. K8 and K18 mRNAs were detected by Northern blot and reverse transcriptase polymerase chain reaction analyses in both lines before BrdU treatment, but no increase in mRNA levels was observed in either cell line over 21 days of treatment. This suggests, firstly, that keratin synthesis is normally blocked at a posttranscriptional level in DLKP and H82 cells, and secondly, that BrdU can reverse this block. A549 is a human lung cell line which contains K8 and K18 proteins. Treatment with BrdU increased K8 and K18 protein levels in these cells. No corresponding increase in K8 mRNA levels occurred, while an apparent increase in K18 mRNA levels was detected. HL-60 is a leukaemic cell-line of haematopoietic rather than epithelial lineage which contains K8 and K18 mRNA transcripts prior to BrdU treatment, but does not contain keratin proteins. Again, K8 and K18 mRNA levels remained unchanged during BrdU treatment. However, neither K8 nor K18 proteins were detected following treatment, although BrdU is known to alter expression of other genes in HL-60 cells. BrdU thus appears to act at a posttranscriptional level and in an epithelial-specific manner to reverse a block in keratin synthesis in keratin-negative lung cancer cells and increase synthesis in keratin-positive lung cancer cells. This may represent a regulatory step in early lung development or a mechanism whereby tumour cells downregulate expression of a differentiated phenotype.
Authors:
S McBride; D Walsh; P Meleady; N Daly; M Clynes
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  64     ISSN:  0301-4681     ISO Abbreviation:  Differentiation     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-25     Completed Date:  1999-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  185-93     Citation Subset:  IM    
Affiliation:
National Cell and Tissue Culture Centre, BioResearch Ireland, Dublin City University, Glasnevin, Ireland. Shirley.McBride@ed.uk
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites, Antineoplastic / pharmacology*
Bromodeoxyuridine / pharmacology*
Carcinoma, Small Cell / drug therapy,  metabolism*
Down-Regulation
Humans
Keratins / biosynthesis*,  drug effects,  genetics
Lung Neoplasms / drug therapy,  metabolism*
Protein Processing, Post-Translational
RNA, Messenger / analysis,  drug effects
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/RNA, Messenger; 59-14-3/Bromodeoxyuridine; 68238-35-7/Keratins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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