Arsenic-induced changes in the gene expression of lung epithelial L2 cells: implications in carcinogenesis.
BACKGROUND
Arsenic is a carcinogen that is known to induce cell transformation and tumor formation. Although studies have been performed to examine the modulation of signaling molecules caused by arsenic exposure, the molecular mechanisms by which arsenic causes cancer are still unclear. We hypothesized that arsenic alters gene expression leading to carcinogenesis in the lung.


RESULTS
In this study, we examined global gene expression in response to 0.75 microM arsenic treatment for 1-7 days in a rat lung epithelial cell line (L2) using an in-house 10 k rat DNA microarray. One hundred thirty one genes were identified using the one-class statistical analysis of microarray (SAM) test. Of them, 33 genes had a fold change of > or = 2 between at least two time points. These genes were then clustered into 5 groups using K-means cluster analysis based on their expression patterns. Seven selected genes, all associated with cancer, were confirmed by real-time PCR. These genes have functions directly or indirectly related to metabolism, glycolysis, cell proliferation and differentiation, and regulation of transcription.


CONCLUSIONS
Our findings provide important insight for the future studies of arsenic-mediated lung cancer.
Posey
Tisha
T
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA. tisha.posey@okstate.edu
Weng
Tingting
T
Chen
Zhongming
Z
Chintagari
Narendranath R
NR
Wang
Pengcheng
P
Jin
Nili
N
Stricker
Heidi
H
Liu
Lin
L
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002454:Cell Differentiation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects; D002478:Cells, Cultured; D016000:Cluster Analysis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats
D002273:Carcinogens; D001151:Arsenic