Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer.
The complex process of carcinogenesis begins with transformation of a single cell to favor aberrant traits such as loss of contact inhibition and unregulated proliferation - features found in every cancer. Despite cancer's widespread prevalence, the early events that initiate cancer remain elusive, and without knowledge of these events cancer prevention is difficult. Here we show that exposure to As, Cr, Ni, or vanadium (V) promotes changes in gene expression that occur in conjunction with aberrant growth. We exposed immortalized human bronchial epithelial cells to one of four metals/metalloid for four to eight weeks and selected transformed clonal populations based upon anchorage independent growth of single cells in soft agar. We detected a metal-specific footprint of cancer-related gene expression that was consistent across multiple transformed clones. These gene expression changes persisted in the absence of the progenitor metal for numerous cell divisions. Our results show that even a brief exposure to a carcinogenic metal may cause many changes in gene expression in the exposed cells, and that from these many changes, the specific change(s) that each metal causes that initiate cancer likely arise.
Nelson Institute of Environmental Medicine, New York University School of Medicine, Department of Environmental Health Sciences, 57 Old Forge Road, Tuxedo, NY 10987, USA.
Hailey A
HA
Clancy
Hong
H
Sun
Lisa
L
Passantino
Thomas
T
Kluz
Alexandra
A
Muñoz
Jiri
J
Zavadil
Max
M
Costa
D001151:Arsenic / Q000009:adverse effects*; D001980:Bronchi / Q000166:cytology; D002273:Carcinogens / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D002857:Chromium / Q000009:adverse effects*; D004847:Epithelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D009532:Nickel / Q000009:adverse effects*; D014639:Vanadium / Q000009:adverse effects*
D002273:Carcinogens; D014639:Vanadium; D002857:Chromium; D009532:Nickel; D001151:Arsenic