LRRC4, a Putative Tumor Suppressor Gene, Requires a Functional Leucine-rich Repeat Cassette Domain to Inhibit Proliferation of Glioma Cells In Vitro by Modulating the Extracellular Signal-regulated Kinase/Protein Kinase B/Nuclear Factor-κB Pathway
| Autor: | Dan Li, Yixin Yang, Qiong Chen, Shourong Shen, Jue Ouyang, Yanhong Zhou, Lan Xiao, Minghua Wu, Hou-De Zhou, Xiaoling Li, Yunlian Tang, Zhaoyang Zeng, He Huang, Kai Gan, Ke Tang, Chen Huang, Guiyuan Li |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
STAT3 Transcription Factor
MAPK/ERK pathway Tumor suppressor gene Proto-Oncogene Proteins c-jun Mutant Apoptosis Nerve Tissue Proteins Leucine-rich repeat Leucine-Rich Repeat Proteins Phosphatidylinositol 3-Kinases Cell Line Tumor Tumor Cells Cultured Humans Genes Tumor Suppressor RNA Messenger Extracellular Signal-Regulated MAP Kinases STAT3 Molecular Biology Protein kinase B Protein Kinase C Cell Proliferation biology Kinase Gene Expression Profiling JNK Mitogen-Activated Protein Kinases Transcription Factor RelA Proteins Articles Cell Biology Enzyme Activation STAT protein biology.protein Cancer research Tetradecanoylphorbol Acetate Mutant Proteins Tumor Suppressor Protein p53 Glioblastoma Proto-Oncogene Proteins c-akt |
| Zdroj: | Molecular Biology of the Cell. 17:3534-3542 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e05-11-1082 |
| Popis: | We have previously reported that the LRRC4 gene, which contains a conserved leucine-rich repeat (LRR) cassette and an immunoglobulin (Ig) IgC2 domain, is associated with glioma suppression both in vitro and in vivo. The present study provides evidence that the conspicuous absence of LRRC4 in high-grade gliomas directly contributes to the increasing tumor grade. The loss of LRRC4 in U251 cells is caused by the loss of homozygosity at chromosome 7q32-ter. It was also found that LRRC4 requires a functional LRR cassette domain to suppress U251 cell proliferation. In the LRR cassette domain, the third LRR motif of the core LRR is found to be indispensable for the function of LRRC4. The inhibitory effect of LRRC4 is accompanied by a decrease in the expression of pERK, pAkt, pNF-κBp65, signal transducer and activator of transcription protein-3 (STAT3), and mutant p53, and an increase in the expression of c-Jun NH2-terminal kinase (JNK)2 and p-c-Jun, suggesting that LRRC4 plays a major role in suppressing U251 cell proliferation by regulating the extracellular signal-regulated kinase (ERK)/Akt/NF-κBp65, STAT3, and JNK2/c-Jun pathways. In conclusion, LRRC4 may act as a novel candidate of tumor suppressor gene. Therefore, the loss of LRRC4 function may be an important event in the progression of gliomas. |
| Databáze: | OpenAIRE |
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