Ding Yi, Wang Gang, Ling Ming Tat, Wong Y C, Li Xin, Na Yanqun, Zhang Xiaomeng, Chua Chee Wai, Wang Xianghong, Xin Dianqi
Cancer Biology Group, Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, PR China.
Int J Oncol. 2006 Apr;28(4):847-54.
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.
表皮生长因子受体（EGFR）被认为是膀胱癌侵袭进展的阳性因素之一。Id-1（分化或DNA结合抑制因子）是一种螺旋-环-螺旋（HLH）转录因子，最近被确定为EGFR信号通路中的关键因子。本研究的目的是探讨Id-1在膀胱癌进展中的作用及其与EGFR的关系。利用不同阶段膀胱癌的临床标本，进行免疫组织化学染色，以确定Id-1表达是否与肿瘤分期和EGFR表达呈正相关。还通过伤口闭合和胶原侵袭试验在RT112膀胱癌细胞系中异位表达Id-1基因，研究了Id-1在癌细胞侵袭中的直接作用。为了探索靶向Id-1基因在侵袭性膀胱癌治疗中的潜力，我们研究了通过小RNA干扰使Id-1基因失活是否能导致MGHU1膀胱癌细胞系侵袭的抑制。我们的结果表明，Id-1的上调与EGFR表达增加、临床分期以及膀胱癌细胞的侵袭能力相关。Id-1的失活可能是抑制膀胱癌细胞侵袭的潜在治疗靶点。
