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PMID:22363646
| Citation |
Zhu, H, Xia, L, Zhang, Y, Wang, H, Xu, W, Hu, H, Wang, J, Xin, J, Gang, Y, Sha, S, Xu, B, Fan, D, Nie, Y and Wu, K (2012) Activating transcription factor 4 confers a multidrug resistance phenotype to gastric cancer cells through transactivation of SIRT1 expression. PLoS ONE 7:e31431 |
|---|---|
| Abstract |
Multidrug resistance (MDR) in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4) is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. |
| Links |
PubMed PMC3281959 Online version:10.1371/journal.pone.0031431 |
| Keywords |
Activating Transcription Factor 4/metabolism; Apoptosis/genetics; Base Sequence; Cell Line, Tumor; DNA Damage; Down-Regulation/genetics; Drug Resistance, Multiple/genetics; Drug Resistance, Neoplasm/genetics; Gene Expression Regulation, Neoplastic; Humans; Molecular Sequence Data; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; P-Glycoprotein/genetics; P-Glycoprotein/metabolism; Phenotype; Promoter Regions, Genetic/genetics; RNA, Small Interfering/metabolism; Sirtuin 1/antagonists & inhibitors; Sirtuin 1/genetics; Sirtuin 1/metabolism; Stomach Neoplasms/genetics; Stomach Neoplasms/pathology; Transcriptional Activation/genetics; Transfection; Up-Regulation/genetics; bcl-2-Associated X Protein/genetics; bcl-2-Associated X Protein/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0042493: response to drug |
ECO:0000315: |
P |
Figure 4: Knockdown of SIRT1 allows the cells to become sensitive to the drug. Data shows that SIRT1 allows the cell to be drug resistant. |
complete | ||||
| GO:0043066: negative regulation of apoptotic process |
ECO:0000270: |
P |
Figure 5A-C: overexpression of SIRT1 allows for the downregulation of apoptosis, allowing for ATF4-induced multi-drug resistance in gastric cancer. |
complete | ||||
| GO:0010467: gene expression |
ECO:0000314: |
P |
Figure 1A: Protein and mRNA levels of ATF4 were determined using Western Blot and qPCR. β-actin and GAPDH were used as a control. |
complete | ||||
| GO:0001558: regulation of cell growth |
ECO:0000315: |
P |
Figure 1B, C, D, E, H: When transfected into SGC7901 and AGS cells, colony number increased due to overexpression of ATF4. When ATF4 was knocked out of expression in SGC7901/ADR and SGC7901/VCR cells the colony number decreased. This shows that ATF4 produced multi-drug resistance in cancer cells, allowing for cell growth. |
complete | ||||
See also
References
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