The carcinogen (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene induces Cdc25B expression in human bronchial and lung cancer cells.
Cdc25B regulates cell cycle progression and genetic stability. Here, we report that exposure to the environmental carcinogen (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) causes a marked increase in the expression of Cdc25B mRNA and protein levels in terminal squamous differentiated human bronchial epithelial cells and in lung cancer cells, but not in undifferentiated bronchial cells. In addition, the growth rate of lung cancer cells was increased significantly in comparison with untreated cells after chronic exposure to 0.1 micro M anti-BPDE. Furthermore, increased Cdc25B expression and decreased Cdk1 phosphorylation were observed in anti-BPDE-treated cells. We postulate that the induction of Cdc25B expression in lung cancer cells by the ultimate carcinogen anti-BPDE accelerates the further development of lung carcinogenesis.
Oguri
Tetsuya
T
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Singh
Shivendra V
SV
Nemoto
Kaoru
K
Lazo
John S
JS
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases / Q000096:biosynthesis* / Q000235:genetics
D002273:Carcinogens; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases