Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines.
Function of PrPC (1-OPRD) in biological activities of gastric cancer cell lines.
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DOI：
10.1111/j.1582-4934.2009.00687.x
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发表时间：
2009-11
影响因子：
5.3
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Liang J;Wang J;Luo G;Pan Y;Wang X;Guo C;Zhang D;Yin F;Zhang X;Liu J;Wang J;Guo X;Wu K;Fan D
约10-15%的人类朊病毒病是遗传性的，其中一个重要的基因突变发生在朊病毒蛋白基因的八肽重复区。其中一个变异体，一个八肽重复缺失（1-OPRD），存在于多种胃癌细胞系中，其突变频率在胃癌病例中较高。然而，它的生物学功能仍然未知。将野生型和突变型PrPC克隆并转染到胃癌细胞中。分别观察细胞凋亡、粘附、侵袭、多药耐药（MDR）和细胞增殖情况。通过基因芯片筛选差异表达基因，并通过PT-PCR进行验证。荧光素酶报告试验进一步检测靶基因的转录激活。强制过表达PrPC（1-OPRD）可促进胃癌细胞SGC 7901的生长，其机制可能与PrPC（1-OPRD）促进细胞周期G1期向S期的转变有关。PrPC（1-OPRD）可抑制SGC 7901细胞凋亡，促进细胞粘附、侵袭和MDR。而野生型PrPC（1-OPRD）与PrPC在细胞凋亡、侵袭和MDR方面无明显差异。进一步的实验表明，PrPC（1-OPRD）除了激活cyclinD 1外，还能激活cyclinD 3的反式激活，从而促进细胞的转化和增殖。PrPC（1-OPRD）过表达可能部分通过转录激活cyclinD 3促进胃癌细胞增殖，加速G1/S期转变。PrPC（1-OPRD）的促增殖作用明显强于野生型PrPC。但对胃癌细胞的凋亡、粘附、侵袭和MDR效应无明显影响。
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 PrPC 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 PrPC (1-OPRD) could promote the gastric cancer cells SGC7901 growth through facilitating G1- to S-phase transition in the cell cycle. PrPC (1-OPRD) could also inhibit apoptosis, and promote adhesion, invasion and MDR in SGC7901. However, it exhibited no significant difference between wild-type PrPC (1-OPRD) and PrPC on apoptosis, invasion or MDR effects. Further experiments indicated that PrPC (1-OPRD) could trigger the transactivation of cyclinD3 besides cyclinD1 to promote cell transition and proliferation. Overexpression of PrPC (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 PrPC (1-OPRD) was more than that of wild-type PrPC. However, they showed no difference on apoptosis, adhesion, invasion or MDR effects of gastric cancer cells.