title: Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells.
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.
authors: Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. mkim51@jhmi.edu
authors: Myoung Sook
authors: MS
authors: Kim
authors: Yiping
authors: Y
authors: Huang
authors: Juna
authors: J
authors: Lee
authors: Xiaoli
authors: X
authors: Zhong
authors: Wei-Wen
authors: WW
authors: Jiang
authors: Edward A
authors: EA
authors: Ratovitski
authors: David
authors: D
authors: Sidransky
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*
chemical_list: D015820:Cadherins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D003847:Deoxyglucose