title: LRIG1 combined with cisplatin enhances bladder cancer lesions via a novel pathway.
abstract: One aspect of chemotherapy insensitivity and resistance results from induction of epidermal growth factor receptor (EGFR) internalization and initial DNA damage repair in response to DNA-damaging stimuli, such as cisplatin (CDDP). Previously, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), as one of the natural ligands of EGFR, could combine with and down-regulate the expression of EGFR in bladder cancer cells. This finding interested us and we hypothesized that LRIG1 could be a novel candidate for facilitating cisplatin-induced bladder cancer cell lesions. To investigate this further, we overexpressed LRIG1 with an adenovirus vector in EJ/T24 bladder cancer cells and investigated total EGFR, nuclear expression of phosphorylated EGFR (pEGFR) and cell lesions with exposure to CDDP. CDDP-induced nuclear pEGFR levels accumulated with time and were decreased by LRIG1 overexpression. LRIG1-transduced cells treated with CDDP had more severe DNA damage, cellular apoptosis, growth inhibition and reversal of invasion. These preclinical studies indicate that LRIG1 may represent a new therapeutic approach to improve the response of bladder cancer to chemotherapy through a novel pathway.
authors: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors: Fan
authors: F
authors: Li
authors: Weimin
authors: W
authors: Yang
authors: Dongsheng
authors: D
authors: Guo
authors: Zhiquan
authors: Z
authors: Hu
authors: Hua
authors: H
authors: Xu
authors: Zhangqun
authors: Z
authors: Ye
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014161:Transduction, Genetic; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; D066246:ErbB Receptors; D002945:Cisplatin