Dataset Information

Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.

ABSTRACT: Nicotine, the major component in cigarette smoke, can promote tumor growth and angiogenesis in various cancers, including lung cancer. Hypoxia-inducible factor-1alpha (HIF-1alpha) is overexpressed in human lung cancers, particularly in non-small cell lung cancers (NSCLC), and is closely associated with an advanced tumor grade, increased angiogenesis, and resistance to chemotherapy and radiotherapy. The purpose of this study was to investigate the effects of nicotine on the expression of HIF-1alpha and its downstream target gene, vascular endothelial growth factor (VEGF), in human lung cancer cells.Human NSCLC cell lines A549 and H157 were treated with nicotine and examined for expression of HIF-1alpha and VEGF using Western blot or ELISA. Loss of HIF-1alpha function using specific small interfering RNA was used to determine whether HIF-1alpha is directly involved in nicotine-induced tumor angiogenic activities, including VEGF expression, cancer cell migration, and invasion.Nicotine increased HIF-1alpha and VEGF expression in NSCLC cells. Pharmacologically blocking nicotinic acetylcholine receptor-mediated signaling cascades, including the Ca2+/calmodulin, c-Src, protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2, and the mammalian target of rapamycin pathways, significantly attenuated nicotine-induced up-regulation of HIF-1alpha protein. Functionally, nicotine potently stimulated in vitro tumor angiogenesis by promoting tumor cell migration and invasion. These proangiogenic and invasive effects were partially abrogated by treatment with small interfering RNA specific for HIF-1alpha.These findings identify novel mechanisms by which nicotine promotes tumor angiogenesis and metastasis and provide further evidences that HIF-1alpha is a potential anticancer target in nicotine-associated lung cancer.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC4166418 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.

Zhang Qunzhou Q Tang Xudong X Zhang Zuo-Feng ZF Velikina Rita R Shi Shihong S Le Anh D AD

Clinical cancer research : an official journal of the American Association for Cancer Research 20070801 16

<h4>Purpose</h4>Nicotine, the major component in cigarette smoke, can promote tumor growth and angiogenesis in various cancers, including lung cancer. Hypoxia-inducible factor-1alpha (HIF-1alpha) is overexpressed in human lung cancers, particularly in non-small cell lung cancers (NSCLC), and is closely associated with an advanced tumor grade, increased angiogenesis, and resistance to chemotherapy and radiotherapy. The purpose of this study was to investigate the effects of nicotine on the expres ...[more]

PMID: 17699846

Similar Datasets

Project description:BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. METHODS: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1alpha and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1alpha splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. RESULTS: HIF-1alpha isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1alphaTAG) and HIF-1alpha736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1alphaTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1alphaTAG (P = 0.048), and total HIF-1alpha (P = 0.048) mRNA levels. HIF-1alphaTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1alphaTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01). CONCLUSIONS: Our results show for the first time that mRNA expression of a HIF-1alphaTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45.

Dataset Information

Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.

Publications

Nicotine induces hypoxia-inducible factor-1alpha expression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets