Effects of silencing of HER2/neu gene in anti-BPDE-transformed cells.
Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a]P) and acts as a potent mutagen in mammalian systems. However, the molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. We have used malignant human bronchial epithelial cells (16HBE-T) transformed by exposure to anti-BPDE to help characterize these possible molecular mechanisms. We have previously observed overexpression of HER2/neu in 16HBE-T. To further investigate the effects of HER2/neu on 16HBE-T cell biologic phenotype, we inhibited HER2/neu expression using RNA interference. Silencing of HER2/neu in 16HBE-T cells was performed in vitro using retrovirus-delivered short hairpin RNA (shRNA). Silencing of HER2/neu in 16HBE-T cells resulted in significant increases and decreases in the proportions of cells in G0/G1 phase (67.1+/-2.1%) and in S phase (17.3+/-4.1%), respectively, and significantly reduced cell viability and colony formation rate. These results may help to explain epithelial cell transformation following exposure to anti-BPDE, and suggest an oncogenic role for HER2/neu in anti-BPDE-induced carcinogenesis.
Jiang
Yiguo
Y
Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical College, 195 Dongfengxi Road, Guangzhou 510182, China. jiangyiguo@yahoo.com
Fu
Juan
J
Greenlee
Anne R
AR
Shen
Yuelan
Y
Duan
Huihan
H
Chen
Xuemin
X
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018734:Genes, erbB-2; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D034622:RNA Interference / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects; D014162:Transfection
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D009153:Mutagens; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human