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Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells
Author(s) -
Kim Myoung Sook,
Huang Yiping,
Lee Juna,
Zhong Xiaoli,
Jiang WeiWen,
Ratovitski Edward A.,
Sidransky David
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25057
Subject(s) - glycolysis , malignant transformation , mitochondrion , vimentin , biology , cancer research , cell growth , microbiology and biotechnology , endocrinology , metabolism , immunology , biochemistry , immunohistochemistry
Abstract Cigarette‐smoking increases the risk of developing various types of human cancers including esophageal cancers. To test the effects of chronic cigarette smoke exposure directly on esophageal epithelium, cellular resistance to mainstream extract (MSE), or sidestream smoke extract (SSE) was developed in chronically exposed nonmalignant Het‐1A cells. Anchorage‐independent growth, in vitro invasion capacity and proliferation of the resistant cells increased compared with the unexposed, sensitive cells. An epithelial marker E‐cadherin was down‐regulated and mesenchymal markers N‐cadherin and vimentin were up‐regulated in the resistant cells. Het‐1A cells resistant to MSE or SSE consumed more glucose, and produced more lactate than the sensitive cells. The increased anchorage‐independent cell growth of the resistant cells was suppressed by a glycolysis inhibitor, 2‐deoxy‐ D ‐glucose, indicating that these cells are highly dependent on the glycolytic pathway for survival. Decreased mitochondrial membrane potential and ATP production in the resistant cells indicate the presence of mitochondrial dysfunction induced by chronic exposure of cigarette smoke extract. Increased expression of nuclear genes in the glycolytic pathway and decreased levels of mitochondrial genes in the resistant cells support the notion that cigarette smoking significantly contributes to the transformation of nonmalignant esophageal epithelial cells into a tumorigenic phenotype.