Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Effect of cigarette smoke on gene expression in mammary epithelial cells [gene expression]

ABSTRACT: Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increases the risk of breast cancer. Little is known, however, about the molecular mechanisms by which tobacco smoke contributes to breast carcinogenesis. To investigate these mechanisms we have analyzed gene expression and methylation in MCF 10A mammary epithelial cells chronically exposed to aqueous cigarette smoke extract (CSE). CSE was prepared weekly and added to the cell cultures at a concentration equivalent to 0.001 cigarettes/ml. Two clones were isolated after 13 weeks of treatment and expanded in the same concentration of CSE for 8 additional weeks. Mock-treated samples were prepared in parallel.

ORGANISM(S): Homo sapiens

SUBMITTER: Francescopaolo Di Cello

PROVIDER: E-GEOD-42667 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells.

Di Cello Francescopaolo F Flowers V Lynn VL Li Huili H Vecchio-Pagán Briana B Gordon Brent B Harbom Kirsten K Shin James J Beaty Robert R Wang Wei W Brayton Cory C Baylin Stephen B SB Zahnow Cynthia A CA

Molecular cancer 20130806

<h4>Background</h4>Recent epidemiological studies demonstrate that both active and involuntary exposure to tobacco smoke increase the risk of breast cancer. Little is known, however, about the molecular mechanisms by which continuous, long term exposure to tobacco smoke contributes to breast carcinogenesis because most previous studies have focused on short term treatment models. In this work we have set out to investigate the progressive transforming effects of tobacco smoke on non-tumorigenic ...[more]

PMID: 23919753

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Project description:Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects. However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear. To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro. Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions. Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6 hr. RNA was extracted immediately or after a 4-hr recovery period and hybridized to mouse whole genome microarrays. Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response. These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure. Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC. In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas m-phase cell cycle pathways were more significantly affected following TSC exposure. MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC. This study shows that in general, MSC impacts many of the same molecular processes as TSC. However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures. Murine epithelial lung cells were exposed to tobacco smoke condensates (0, 25, 50, 90 Î¼g/ml) or marijuana smoke condensates (0, 2.5, 5, 10 Î¼g/ml) in serum-free medium for a six hour period. Following the six-hour exposure, cells were either harvested immediately or washed with phosphate-buffered saline and incubated in fresh serum-free medium for a four hour recovery period. Total RNA was extracted from the cells and hybridized against Universal Mouse Reference RNA (Agilent Technologies Canada, Inc.) to Agilent whole mouse genome microarray slides containing 44,000 transcripts. A LOWESS normalization was applied to expression results, and statistically significant genes were identified using the R library MAANOVA. Microarray results were validated by real time RT-PCR.

Dataset Information

Effect of cigarette smoke on gene expression in mammary epithelial cells [gene expression]

Publications

Cigarette smoke induces epithelial to mesenchymal transition and increases the metastatic ability of breast cancer cells.

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