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BRD7 suppresses the growth of Nasopharyngeal Carcinoma cells (HNE1) through negatively regulating β-catenin and ERK pathways

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Abstract

BRD7 is a novel gene which involved NPC in our lab. Our previous studies showed that BRD7 was expressed at high level in normal nasopharyngeal epithelial tissues, but at low level in nasopharyngeal carcinoma biopsies and cell lines. In these papers, we found that ectopic expression of BRD7 can decrease cell proliferation and capability to form colonies in soft agar. FCM (Flow cytometry) assay indicated that the cell cycle progression from G1 to S phase was inhibited and the expression of cyclinD1 was significantly decreased after being transfected with BRD7 in HNE1 cells (NPC cells). To further investigate the molecular mechanism of BRD7 suppression of NPC cells growth, the cDNA microarray was performed to detect difference in gene expression profile induced by BRD7. The results indicated that 21 genes expression were changed after being transfected with BRD7 and the differentially expressed gene including α-catenin, cyclinD1, E2F3 was confirmed by western-blot. Next, we found that even though no obvious changes of the total expression of β-catenin were observed, the accumulation of β-catenin in nucleus was blocked. In addition, it was found that the expression of β-catenin was up-regulated in the complex composed of β-catenin and α-catenin in HNE1 cells induction of BRD7. So, we concluded that over-expression of BRD7 increased the expression of α-catenin which “hold” β-catenin in the complex and inhibited its accumulating in nucleus. At last, we demonstrated the c-jun, p-MEK, and p-ERK1/2 expression were down-regulated, and the Ap-1 promoter activity was inactive after being transfected with BRD7. We also found that over-expression of BRD7 can inactivate the c-jun and p-ERK1/2 after being treated with EGF in HNE1 cells. These results indicated that BRD7 played a negative role in ERK1/2 pathway. Taken together, our present results provide new insights for BRD7 function to inhibit NPC cells growth through negative regulating β-catenin and ERK1/2 pathways.

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Acknowledgments

We are grateful to Dr. J.J. Li for his kind provision of AP1 reporter plasmid luciferase reporter plasmid. This work is supported by grants from the National Natural Science Foundation of China (30400528; 30400238; 30470367.) and Hunan Natural Scientific Foundation of China (04JJ3097)

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Authors and Affiliations

  1. Cancer Research Institute, Central South University, Changsha, Hunan, 410078, China

    Cong Peng, Hua Ying Liu, Ming Zhou, Li Ming Zhang, Xiao Ling Li & Gui Yuan Li

  2. The Third Xiang Ya Hospital, Central South University, Changsha, Hunan, China

    Shou Rong Shen

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  1. Cong Peng
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  2. Hua Ying Liu
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  3. Ming Zhou
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  4. Li Ming Zhang
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  7. Gui Yuan Li
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Correspondence to Gui Yuan Li.

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Peng, C., Liu, H.Y., Zhou, M. et al. BRD7 suppresses the growth of Nasopharyngeal Carcinoma cells (HNE1) through negatively regulating β-catenin and ERK pathways. Mol Cell Biochem 303, 141–149 (2007). https://doi.org/10.1007/s11010-007-9466-x

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  • DOI: https://doi.org/10.1007/s11010-007-9466-x

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