Acta Pharmacologica Sinica (2009) 30: 1543–1549; doi: 10.1038/aps.2009.149

Acta Pharmacologica Sinica (2009) 30: 1543–1549; doi: 10.1038/aps.2009.149

Original Article

Orphan nuclear receptor Nur77 is required for the differentiation of C6 glioma cells induced by cholera toxin

Dong XU¹, Yi-jun HUANG¹, Yan LI¹, Wei YIN², Guang-mei YAN^1,*

¹Departments of Pharmacology and ²Biochemistry, Zhong-shan Medical College, Sun Yat-Sen University, Guangzhou 510089, China

Aim: To investigate a possible regulator gene involved in the cholera toxin-induced differentiation of rat C6 glioma cells.

Methods: The global changes in the mRNA expression pattern induced by cholera toxin were analyzed using gene chip microarray. The selected gene was then silenced by RNA interference or overexpressed with an ORF plasmid to determine its necessity in this process.

Results: Nur77, a member of the orphan nuclear receptor family (NR 4A ), was markedly up-regulated during the process of differentiation. Furthermore, RNAi of nur77 attenuated the induction effect of cholera toxin on C6 cells, whereas overexpression of nur77 led to similarly differentiated behavior, including morphologic and biomarker changes, as well as cell cycle arrest.

Conclusion: Nur77 participated actively and essentially as an important regulator in the cholera toxin-induced differentiation of C6 cells.

Keywords: cholera toxin; malignant glioma; differentiation; orphan nuclear receptor; nur77

Project was supported by National Natural Science Foundation of China, Key program (No 30830111).

^# The first two authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail ygm@mail.sysu.edu.cn
Received 2009-05-25 Accepted 2009-09-10

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