title: Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells.
abstract: The transcription factor Early Growth Response-1 (EGR-1) is overexpressed in human prostate tumors and contributes to prostate cancer progression through an unknown mechanism. Here we report that EGR-1 transcriptionally regulates the expression of insulin-like growth factor-1 receptor (IGF-1R), which is highly expressed in primary prostate cancer. We find that ectopic expression of EGR-1 causes increase in IGF-1R expression, while knockdown of EGR-1 leads to dramatically decrease in IGF-1R expression. Results from chromatin immunoprecipitation (ChIP) and reporter assay show that the EGR-1 directly binds to the human IGF-1R gene and triggers the target gene expression. EGR-1 activates Erk and Akt pathway through regulation of IGF-1R, and thus promote prostate cancer cell growth. Taken together, these results suggest that EGR-1 may stimulate prostate cancer cell growth through up-regulation of IGF-1R and indicate that down-regulation of EGR-1 could be an effective therapeutic approach against prostate cancer.
authors: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors: Yang
authors: Y
authors: Ma
authors: Qinqin
authors: Q
authors: Cheng
authors: Zijia
authors: Z
authors: Ren
authors: Lu
authors: L
authors: Xu
authors: Ying
authors: Y
authors: Zhao
authors: Jie
authors: J
authors: Sun
authors: Siyi
authors: S
authors: Hu
authors: Weihua
authors: W
authors: Xiao
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D020121:5' Untranslated Regions; D051766:Early Growth Response Protein 1; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases