Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial cells.
Reciprocal effects of NNK and SLURP-1 on oncogene expression in target epithelial cells.
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DOI：
10.1016/j.lfs.2012.02.004
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发表时间：
2012-11-27
期刊：
影响因子：
6.1
通讯作者：
Grando, Sergei A.
中科院分区：
文献类型：
--
作者：
Kalantari-Dehaghi, Mina;Bernard, Hans-Ulrich;Grando, Sergei A.
关键词：
阐明烟草亚硝胺（4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮）（NNK）靶向的支气管和口腔上皮细胞上表达的烟碱乙酰胆碱受体如何促进致癌转化。由于NNK依赖性转化可被烟碱能分泌的哺乳动物Ly-6/尿激酶纤溶酶原激活物受体相关蛋白-1（SLURP-1）消除，我们比较了NNK和重组（r）SLURP-1分别对人永生化支气管和口腔上皮细胞系BEP-2D和Het-1A中肿瘤发生相关基因表达的影响。NNK刺激致癌基因的表达，包括BEP2D中的MYB和PIK3CA，Het-1A中的ETS1、NRAS和SRC，以及两种细胞类型中的AKT1、KIT和RB1，这些基因在rSLURP-1存在下可以被消除。NNK上调的其他癌症相关基因可被rSLURP-1消除，这些基因是BEP2D细胞中的生长因子EGF和Het-1A细胞中的HGF，以及转录因子CDKN 2A和STAT 3（仅Het-1A）。NNK还上调抗凋亡BCL 2（Het-1A）并下调促凋亡TNF（Het-1A）、BAX和CASP 8（BEP2D），所有这些都可以被rSLURP-1部分消除。NNK降低了编码细胞间粘附分子β-连环蛋白（BEP2D）的CTNNB 1基因的表达，以及BEP2D细胞中的肿瘤抑制因子CDKN 3和FOXD 3，Het-1A细胞中的SERPINB 5和两种细胞类型中的RUNX 3。NNK的这些促癌作用也被rSLURP-1消除。所获得的结果确定了NNK和SLURP-1的靶基因，并阐明了它们对支气管和口腔上皮细胞致瘤性转化的相互作用的分子机制。
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. 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 BEP-2D and Het-1A, respectively. 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, SERPINB5 in Het-1A cells, and RUNX3 in both cell types. These pro-oncogenic effects of NNK were also abolished by rSLURP-1. 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.
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影响因子：
10.4
作者：
HECHT, SS;CARMELLA, SG;PETERSON, LA
通讯作者：
PETERSON, LA
影响因子：
11.5
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影响因子：
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