Yonsei Med J.  2014 Sep;55(5):1196-1205. 10.3349/ymj.2014.55.5.1196.

LRIG1 Enhances Chemosensitivity by Modulating BCL-2 Expression and Receptor Tyrosine Kinase Signaling in Glioma Cells

• Guo Z
• Chen Q
• Liu B
• Tian D
• Zhang S
• Li M

• KMID: 1799481
• DOI: http://doi.org/10.3349/ymj.2014.55.5.1196

Abstract

PURPOSE
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent years, and many studies showed that LRIG1 is a tumor suppressor gene and may be related to tumor drug resistance. In this study, we explored whether LRIG1 protein expression can improve the chemosensitivity of glioma cells and what was its mechanism.
MATERIALS AND METHODS
We collected 93 cases of glioma tissues and detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we changed the expression of LRIG1 and BCL-2 and explored the relationship between LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and RTKs.
RESULTS
LRIG1 was negatively correlated with BCL-2 expression in glioma tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity and inhibit BCL-2 expression. Furthermore, LRIG1 was negatively correlated with RTKs in U251/MDR cells.
CONCLUSION
These results demonstrated that LRIG1 can improve chemosensitivity by modulating BCL-2 expression and RTK signaling in glioma cells.

Keyword

Glioma; LRIG1; chemosensitivity; BCL-2; RTKs

MeSH Terms

Astrocytoma/drug therapy/genetics/metabolism
Cell Line, Tumor
Drug Resistance, Neoplasm/genetics/*physiology
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioma/drug therapy/*metabolism
Humans
Membrane Glycoproteins/metabolism/*physiology
Proto-Oncogene Proteins c-bcl-2/*metabolism
RNA, Messenger/metabolism
Receptor Protein-Tyrosine Kinases/metabolism
Membrane Glycoproteins
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Receptor Protein-Tyrosine Kinases

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