Document Detail


Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial cells.
MedLine Citation:
PMID:  22369755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: To elucidate how the nicotinic acetylcholine receptors expressed on bronchial and oral epithelial cells targeted by the tobacco nitrosamine (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) facilitate carcinogenic transformation.
MAIN METHODS: Since NNK-dependent transformation can be abolished by the nicotinergic secreted mammalian Ly-6/urokinase plasminogen activator receptor related protein-1 (SLURP-1), we compared effects of NNK and recombinant (r)SLURP-1 on the expression of genes related to tumorigenesis in human immortalized bronchial and oral epithelial cell lines BEP2D and Het-1A, respectively.
KEY FINDINGS: NNK stimulated expression of oncogenic genes, including MYB and PIK3CA in BEP2D, ETS1, NRAS and SRC in Het-1A, and AKT1, KIT and RB1 in both cell types, which could be abolished in the presence of rSLURP-1. Other cancer-related genes whose upregulation by NNK was abolishable by rSLURP-1 were the growth factors EGF in BEP2D cells and HGF in Het-1A cells, and the transcription factors CDKN2A and STAT3 (Het-1A only). NNK also upregulated the anti-apoptotic BCL2 (Het-1A) and downregulated the pro-apoptotic TNF (Het-1A), BAX and CASP8 (BEP2D), all of which could be abolished, in part, by rSLURP-1. NNK decreased expression of the CTNNB1 gene encoding the intercellular adhesion molecule β-catenin (BEP2D), as well as tumor suppressors CDKN3 and FOXD3 in BEP2D cells and SERPINB5 in Het-1A cells. These pro-oncogenic effects of NNK were abolished by rSLURP-1 that also upregulated RUNX3.
SIGNIFICANCE: The obtained results identified target genes for both NNK and SLURP-1 and shed light on the molecular mechanism of their reciprocal effects on tumorigenic transformation of bronchial and oral epithelial cells.
Authors:
Mina Kalantari-Dehaghi; Hans-Ulrich Bernard; Sergei A Grando
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-20
Journal Detail:
Title:  Life sciences     Volume:  91     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-01-24     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1122-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Dermatology, University of California, Irvine, CA 92697, USA.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Ly / metabolism*
Bronchi / cytology,  drug effects,  metabolism,  pathology
Carcinogens / metabolism
Cell Line, Tumor
Cell Transformation, Neoplastic / chemically induced*,  genetics*,  metabolism
Epithelial Cells / drug effects,  metabolism,  pathology*
Gene Expression Regulation, Neoplastic* / drug effects
Humans
Lung Neoplasms / chemically induced,  genetics,  metabolism,  pathology
Mouth / cytology,  drug effects,  metabolism,  pathology
Mouth Neoplasms / chemically induced,  genetics,  metabolism,  pathology
Nitrosamines / adverse effects*,  metabolism
Urokinase-Type Plasminogen Activator / metabolism*
Grant Support
ID/Acronym/Agency:
DE14173/DE/NIDCR NIH HHS; ES017009/ES/NIEHS NIH HHS; R01 DE014173-01A1/DE/NIDCR NIH HHS; R01 ES017009/ES/NIEHS NIH HHS; R01 ES017009-01A2/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/ARS protein, human; 0/Antigens, Ly; 0/Carcinogens; 0/Nitrosamines; 64091-91-4/4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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