沉默的选定谷氨酸受体亚基调节肿瘤生长。

Silencing of selected glutamate receptor subunits modulates cancer growth.

机构信息

Department of Pediatric Neurology, Children's Hospital, University of Technology, Dresden, Germany.

出版信息

Anticancer Res. 2011 Oct;31(10):3181-92.

PMID:21965725

Abstract

BACKGROUND

Emerging evidence supports a role for glutamate in the biology of cancer. We studied the impact of glutamate receptor subunit silencing on cancer phenotype.

MATERIALS AND METHODS

Different fragments of the coding region for ionotropic glutamate receptor AMPA 4 (GLUR4), ionotropic glutamate receptor N-methyl D-aspartate 1 (NR1), ionotropic glutamate receptor kainate 5 (KA2) and ionotropic glutamate receptor N-methyl D-aspartate 2D (NR2D) were stably transfected into human TE671, RPMI8226 and A549 cell lines. Resulting changes in cell proliferation, migration and mRNA expression of genes that determine cancer phenotype were assayed.

RESULTS

Decreased expression of GLUR4 markedly increased cancer cell proliferation, whereas decreased expression of NR1 markedly reduced the propensity of cancer cells to proliferate. Knockdown of KA2 and NR2D did not influence cancer phenotype. Gene silencing of GLUR4 modulated the mRNA expression of various genes in these cancer cell lines, as determined with the Human Cancer PathwayFinder™ PCR Array. Knockdown of GLUR4 influenced the expression and function of genes involved in invasion and metastasis, tumour suppressor genes, oncogenes and adhesion genes.

CONCLUSION

The findings suggest that glutamate receptor subunits on cancer cells are linked to biochemical pathways that regulate malignant phenotype.

摘要

背景

新出现的证据支持谷氨酸在癌症生物学中的作用。我们研究了谷氨酸受体亚基沉默对癌症表型的影响。

材料与方法

将离子型谷氨酸受体 AMPA4（GLUR4）、离子型谷氨酸受体 N-甲基-D-天冬氨酸 1（NR1）、离子型谷氨酸受体 kainate 5（KA2）和离子型谷氨酸受体 N-甲基-D-天冬氨酸 2D（NR2D）的编码区的不同片段稳定转染到人类 TE671、RPMI8226 和 A549 细胞系中。检测了细胞增殖、迁移和决定癌症表型的基因的 mRNA 表达的变化。

结果

GLUR4 的表达降低显著增加了癌细胞的增殖，而 NR1 的表达降低则显著降低了癌细胞增殖的倾向。KA2 和 NR2D 的敲低对癌症表型没有影响。GLUR4 的基因沉默调节了这些癌细胞系中各种基因的 mRNA 表达，这是通过人类癌症途径发现者™ PCR 阵列确定的。GLUR4 的敲低影响了参与侵袭和转移、肿瘤抑制基因、癌基因和粘附基因的表达和功能的基因。