Title : Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial cells - Kalantari-Dehaghi_2012_Life.Sci_91_1122
Author(s) : Kalantari-Dehaghi M , Bernard HU , Grando SA
Ref : Life Sciences , 91 :1122 , 2012
Abstract :

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 beta-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.

PubMedSearch : Kalantari-Dehaghi_2012_Life.Sci_91_1122
PubMedID: 22369755

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Citations formats

Kalantari-Dehaghi M, Bernard HU, Grando SA (2012)
Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial cells
Life Sciences 91 :1122

Kalantari-Dehaghi M, Bernard HU, Grando SA (2012)
Life Sciences 91 :1122