Significance of Id-1 up-regulation and its association with EGFR in bladder cancer cell invasion.
Epidermal growth factor receptor (EGFR) is suggested to be one of the positive factors in the invasive progression of bladder cancer. Id-1 (inhibitor of differentiation or DNA binding), a helix-loop-helix (HLH) transcription factor, was recently identified as a key factor in the EGFR signalling pathway. The aim of this study was to investigate the role of Id-1 in bladder cancer progression and its relation-ship with EGFR. Using clinical specimens from different stages of bladder cancer, immunohistochemical staining was performed to determine if Id-1 expression was positively associated with tumour staging and EGFR expression. The direct role of Id-1 in cancer cell invasion was also investigated through ectopically expressing the Id-1 gene in a RT112 bladder cancer cell line by wound closure and collagen invasion assays. To explore the therapeutic potential of targeting the Id-1 gene in the treatment of invasive bladder cancer, we studied if inactivation of the Id-1 gene through small RNA interference could lead to the suppression of invasion in a MGHU1 bladder cancer cell line. Our results showed that the up-regulation of Id-1 was associated with increased EGFR expression, clinical staging and the invasion ability of bladder cancer cells. Inactivation of Id-1 may be a potential therapeutic target to inhibit the invasion by bladder cancer cells.
Ding
Yi
Y
Cancer Biology Group, Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, PR China.
Wang
Gang
G
Ling
Ming Tat
MT
Wong
Y C
YC
Li
Xin
X
Na
Yanqun
Y
Zhang
Xiaomeng
X
Chua
Chee Wai
CW
Wang
Xianghong
X
Xin
Dianqi
D
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D066246:ErbB Receptors