Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines.
Approximately 10-15% of the human prion disease is inherited and one of the important genetic mutations occurs in the octapeptide repeat region of prion protein gene. One of the variants, one octapeptide repeat deletion (1-OPRD), existed in several gastric cancer cell lines and its mutation frequency was higher in gastric cancer cases. However, the biological functions of it remain unknown. Wild-type and mutation forms of PrP(C) were cloned and transfected into gastric cancer cells. Cell apoptosis, adhesion, invasion, multidrug resistance (MDR) and proliferation were, respectively, investigated. Different expressed genes were screened by gene array and proved by PT-PCR. Further, luciferase report assay was used to explore the transcriptional activation of target genes. Forced overexpression PrP(C) (1-OPRD) could promote the gastric cancer cells SGC7901 growth through facilitating G1- to S-phase transition in the cell cycle. PrP(C) (1-OPRD) could also inhibit apoptosis, and promote adhesion, invasion and MDR in SGC7901. However, it exhibited no significant difference between wild-type PrP(C) (1-OPRD) and PrP(C) on apoptosis, invasion or MDR effects. Further experiments indicated that PrP(C) (1-OPRD) could trigger the transactivation of cyclinD3 besides cyclinD1 to promote cell transition and proliferation. Overexpression of PrP(C) (1-OPRD) might promote the proliferation of gastric cancer cells at least partially through transcriptional activation of cyclinD3 to accelerate the G1-/S-phase transition. The promoting proliferation effect of PrP(C) (1-OPRD) was more than that of wild-type PrP(C). However, they showed no difference on apoptosis, adhesion, invasion or MDR effects of gastric cancer cells.
Liang
Jie
J
State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Wang
Jingbo
J
Luo
Guanhong
G
Pan
Yanglin
Y
Wang
Xin
X
Guo
Changcun
C
Zhang
Dexin
D
Yin
Fang
F
Zhang
Xiaoyin
X
Liu
Jie
J
Wang
Jianhong
J
Guo
Xuegang
X
Wu
Kaichun
K
Fan
Daiming
D
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005453:Fluorescence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
D000970:Antineoplastic Agents; D056743:Cyclin D3; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions