Knockdown of growth-arrest-specific gene 7b (gas7b) using short-hairpin RNA desensitizes neuroblastoma cells to cisplatin: Implications for preventing apoptosis of neurons.
Efficient control of cell survival and cell proliferation is critical for the development of neuron cells. Earlier, we observed that growth arrest-specific gene 7 (Gas7) plays a role in controlling neuritogenesis in mammals. In the present study, we report that the Gas7b isoform is involved in controlling growth arrest and apoptosis of neuroblastoma cells in response to various stimuli. Accordingly, knockdown of Gas7b using small-hairpin RNA (shRNA) was shown to reduce apoptosis induced either by serum starvation or by the antineoplastic agents cisplatin and nocodazole in human neuroblastoma SH-SY5Y cells. Gas7b knockdown also enhanced the ability of the treated cells to form clones in response to cisplatin. On the other hand, forced expression of Gas7a or Gas7b isoform in mouse neuroblastoma Neuro2A cells, which express a defective Gas7 gene, rendered the cells proapoptotic and vulnerable to cisplatin-induced apoptosis. In addition, Neuro2A cells that overexpressed Gas7 showed a reduced ability to form clones. Overexpression of Gas7 produced similar but less extensive effects in nonneuronal HEK293 cells. Taken together, our observations suggest that Gas7b is involved not only in neuritogenesis but also in the regulation of neuronal cell death.
Hung
Feng-Chun
FC
Department of Biochemistry and Molecular Biology, Graduate Institute of Biomedical Sciences, Chang Gung University, Gueishan, Taoyuan, Taiwan, Republic of China. cckchao@mail.cgu.edu.tw
Chao
Chuck C-K
CC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C114909:GAS7 protein, human; C485435:Gas7 protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D002945:Cisplatin