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Research Paper
Hypoxia Induced Overexpression of PrPC in Gastric Cancer Cell Lines
Jie Liang, Feihu Bai, Guanhong Luo, Jingbo Wang, Jingmei Liu, Fulin Ge, Yanglin Pan, Liping Yao, Rui Du, Xiaohua Li, Rui Fan, Hongbo Zhang, Xuegang Guo, Kaichun Wu and Daiming Fan
volume 6 | issue 5
May 2007Pages: 769 - 774
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Cellular prion protein (PrPC), a copper-binding glycosyl-phosphatidylinositol (GPI)-anchored membrane protein that is expressed predominantly in neurons can be induced in ischemia/hypoxic brain tissues. It was also found to be overexpressed and conferred multidrug resistance, promoting cancer metastasis and inhibiting apoptosis in gastric cancer in our lab. In solid tumors, hypoxia can promote malignant progression and confer resistance to chemotherapy by altering gene expression. In present study, we investigated the molecular mechanisms and signaling pathway involved in the induction of the PrPC gene by hypoxia in cancer cell lines. PrPC was detected to be upregulated in several cancer cell lines at both mRNA and protein level, and then found to be induced by hypoxia in a time-dependent manner. After hypoxia treatment, gastric cancer MKN28 cells transfected with luciferase reporter constructs of the human PrPC promoter, which contained HSE, expressed higher luciferase activities (4.3-fold) than those cells transfected with the constructs containing no HSE. In addition, the upregulation of PrPC was reduced by MERK/ERK inhibitor (PD98059). siRNA knockdown of PrPC could make the cells more sensitive to hypoxia induced drug sensitivity. In conclusion, from these findings, we can propose that some transcriptional factors phosphorylated by ERK1/2, could in turn interact with HSE in the promoter of PrPC resulting in upregulation of PrPC in gastric cancer cell line MKN28 during hypoxia. Downregulation of PrPC makes gastric cancer cells more sensitive to hypoxia induced drug sensitivity. However, other mechanisms might also be responsible for hypoxia induced overexpression of PrPC in gastric cancer.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.