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Retrovirus-mediated transduction of a short hairpin RNA gene for GRP78 fails to downregulate GRP78 expression but leads to cisplatin sensitization in HeLa cells.
MedLine Citation:
PMID:  21225231     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Glucose-regulated protein 78 (GRP78) is expressed abundantly in various types of cancer cells and is believed to contribute to chemotherapeutic resistance. In this study, we investigated the effect of a continuous approach for the expression of a short hairpin RNA (shRNA) targeted to GRP78 with retrovirus transduction on the sensitivity to the anticancer drugs VP-16 and cisplatin. The reduction of GRP78 expression failed, and the expression of GRP94 and P5 chaperon mRNA increased; this increase was associated with a mild activation of the unfolded protein response in HeLa cells, which were stably transduced with GRP78 shRNA gene. The transduced cells exhibited similar sensitivity to VP-16-induced cell death when compared to control GFP shRNA gene-transduced cells. However, sensitivity to cisplatin-induced cell death was higher in GRP78 shRNA gene-transduced cells compared to control cells. These results demonstrate that the continuous or prolonged approach targeting GRP78 confers sensitization of HeLa cells to cisplatin independently of the down-regulation of GRP78 expression. The role of the unfolded protein response in sensitization to cisplatin is discussed.
Authors:
Toshikazu Suzuki; Jun Lu; Gaofeng Hu; Kazuko Kita; Nobuo Suzuki
Publication Detail:
Type:  Journal Article     Date:  2011-01-10
Journal Detail:
Title:  Oncology reports     Volume:  25     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-01-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  879-85     Citation Subset:  IM    
Affiliation:
Department of Health and Nutrition, Wayo Women's University, 2-3-1 Konodai, Ichikawa, Chiba 272-8533, Japan.
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