Document Detail

Differential induction of early response genes by adrenomedullin and transforming growth factor-beta1 in human lung cancer cells.
MedLine Citation:
PMID:  12168820     Owner:  NLM     Status:  MEDLINE    
Adrenomedullin (AM) is a hypotensive polypeptide that has been shown to stimulate cyclic AMP and intracellular free Ca2+ agents that are known to induce expression of proto-oncogenes, in various cell types. Transforming growth factor-beta 1 (TGF-beta1) is a multifunctional polypeptide that regulates proliferation, differentiation and cell cycle progression in both normal and malignant epithelial cells. The diverse biological actions of AM and TGF-beta1 may be related to their capacities to initiate different genomic programs in target cells via the induction of expression of multiple genes including early response genes and proto-oncogenes. AM, TGF-beta1 and phorbol-12-myristate-13-acetate (PMA) exert both positive and negative effects on mitogenesis. The effects of AM, TGF-beta1 and PMA were examined in human non-small cell lung cancer (NSCLC) cells. AM caused an increase in its mRNA transcript that peaked by 6 hours and persisted to 24 hours. While expression of TGF-beta1 mRNA was not affected by AM in these cells, the mRNAs for TGF-beta1 and TGF-beta3 decreased by 3 hours. In contrast, TGF-beta1 had no effect on expression of AM mRNA. Interestingly, PMA caused an increase in AM and TGF-beta1 mRNAs in NSCLC cells. While both TGF-beta1 and PMA caused a transient increase in expression of the mRNAs for early response genes including c-fos, c-jun and egr-1 that peaked by 1 hour following treatment, the increase in expression of these mRNAs following treatment with AM peaked only after 3-6 hours. Western blotting analysis showed increases in the levels of c-jun protein following treatment with AM, TGF-beta1 and PMA. The increase in c-jun protein from treatment with AM occurred 10 hours after that from TGF-beta1 and PMA. Activator protein 1 (AP-1) DNA binding activity was also demonstrated to increase following treatment with AM, TGF-beta1 and PMA, with the increase in AP-1 DNA binding activity following AM treatment occurring 10 hours later than that from TGF-beta1 and PMA treatment. These data show that AM can regulate expression of its mRNA transcript in NSCLC cells. Our study suggests that NSCLC cells are important targets of AM and TGF-beta1 and that AM and TGF-beta1 may regulate activities in these malignant lung cells through differential induction of various early response genes.
Stephanie Kane; Margaret A Prentice; Jennifer M Mariano; Frank Cuttitta; Sonia B Jakowlew
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  22     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2002 May-Jun
Date Detail:
Created Date:  2002-08-09     Completed Date:  2002-09-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1433-44     Citation Subset:  IM    
National Cancer Institute, Cell and Cancer Biology Branch, Rockville, Maryland 20850, USA.
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MeSH Terms
Carcinoma, Non-Small-Cell Lung / drug therapy,  genetics*,  metabolism
Gene Expression Regulation, Neoplastic / drug effects*
Genes, Immediate-Early / drug effects*,  genetics
Lung Neoplasms / drug therapy,  genetics*,  metabolism
Peptides / genetics,  metabolism,  pharmacology*
RNA, Messenger / biosynthesis,  genetics
Tetradecanoylphorbol Acetate / pharmacology
Transforming Growth Factor beta / biosynthesis,  genetics,  pharmacology*
Transforming Growth Factor beta1
Tumor Cells, Cultured
Reg. No./Substance:
0/Peptides; 0/RNA, Messenger; 0/TGFB1 protein, human; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 148498-78-6/Adrenomedullin; 16561-29-8/Tetradecanoylphorbol Acetate

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