Differential expression of calcium-related genes in gastric cancer cells transfected with cellular prion protein.
The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein.
Liang
Jie
J
State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Luo
Guanhong
G
Ning
Xiaoxuan
X
Shi
Yongquan
Y
Zhai
Huihong
H
Sun
Shiren
S
Jin
Haifeng
H
Liu
Zhenxiong
Z
Zhang
Faming
F
Lu
Yuanyuan
Y
Zhao
Yunping
Y
Chen
Xiong
X
Zhang
Hongbo
H
Guo
Xuegang
X
Wu
Kaichun
K
Fan
Daiming
D
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D018621:PrPC Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection
C491778:CACYBP protein, human; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D009363:Neoplasm Proteins; D018621:PrPC Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D009418:S100 Proteins; D002118:Calcium