Global gene expression profiling of hyperkeratotic skin lesions from inner Mongolians chronically exposed to arsenic.
The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in their drinking water for >20 years. Gene expression profiling was performed on RNA isolated from 7 individuals in this group and from 4 lesion-free skin samples from healthy individuals. Consistent with the pathological characteristics of the HK lesions, major functional categories and known canonical pathways represented by altered transcripts include those involved in development, differentiation, apoptosis, proliferation, and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term As exposure in the skin.
US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Kathryn
K
Bailey
Yajuan
Y
Xia
William O
WO
Ward
Geremy
G
Knapp
Jinyao
J
Mo
Judy L
JL
Mumford
Russell D
RD
Owen
Sheau-Fung
SF
Thai
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001151:Arsenic / Q000633:toxicity; D020261:Arsenic Poisoning / Q000235:genetics* / Q000473:pathology; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002273:Carcinogens / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D003599:Cytoskeleton / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007642:Keratosis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
D002273:Carcinogens; D051155:Wnt1 Protein; D051176:beta Catenin; D020928:Mitogen-Activated Protein Kinases; D001151:Arsenic