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学科主题: 基础医学
题名:
The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line
作者: Li, MS1; Li, PF1; He, SP1; Du, GG1; Li, G1
刊名: WORLD JOURNAL OF GASTROENTEROLOGY
发表日期: 2002-06-01
卷: 8, 期:3, 页:469-475
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: HUMAN HEPATOCELLULAR-CARCINOMA ; GENE-EXPRESSION ; FETAL HEPATOCYTES ; BINDING-PROTEINS ; DOWN-REGULATION ; MESSENGER-RNA ; TUMOR-CELLS ; IN-VITRO ; PROLIFERATION ; ACID
英文摘要:

AIM: The goal of this study was to characterize the AFP receptor, its possible signal transduction pathway and its proliferative functions in human hepatoma cell line Bel 7402.

METHODS: Cell proliferation enhanced by AFP was detected by MTT assay, H-3-thymidine incorporation and S-stage percentage of cell cycle analysis. With radioactive labeled I-125-AFP for receptor binding assay; cAMP accumulation, protein kinase A activity were detected by radioactive immunosorbent assay and the change of intracellular free calcium ([ Ca2+](i)) was monitored by scanning fluorescence intensity under TCS-NT confocal microscope. The expression of oncogenes N- ras, p53, and p21(ras) in the cultured cells in vitro were detected by Northern blotting and Western blotting respectively.

RESULTS: It was demonstrated that AFP enhanced the proliferation of human hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay, H-3-thymidine incorporation and S-phase percentage up to 2-fold. Two subtypes of AFP receptors were identified in the cells with Kds of 1.3 x 10(-9) mol.L-1 and 9.9 x 10(-8) mol.L-1 respectively. Pretreatment of cells with AFP resulted. in a significant increase (625 %) in cAMP accumulation. The activity of protein kinase A activity were increased up to 37.5, 122.6, 73.7 and 61. 2 % at treatment time point 2, 6, 12 and 24 hours, The level of intracellular calcium were elevated after the treatment of alpha-fetoprotein and achieved to 204 % at 4 min, The results also showed that AFP (20 mg.L-1) could upregulate the expression of N-m oncogenes and p53 and p21(ras) in Bel 7402 cells. In the later case, the alteration were 81. 1 % (12 h) and 97.3 % (12 h) respectively compared with control.

CONCLUSION: These results demonstrate that AFP is potential growth factor to promote the proliferation of human hepatoma Bel 7402 cells. Its growth-regulatory effects are mediated by its specific plasma membrane receptors coupled with its transmembrane signaling transduction through the pathway of cAMP-PKA and intracellular calcium to regulate the expression of oncogenes.

语种: 英语
WOS记录号: WOS:000176452700017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51877
Appears in Collections:基础医学院_生物物理学系_期刊论文

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作者单位: 1.Hainan Med coll, Dept Biochem, Haikou 571101, Hainan, Peoples R China
2.Peking Univ, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100083, Peoples R China
3.Peking Univ, Dept Biophys, Hlth Sci Ctr, Beijing 100083, Peoples R China

Recommended Citation:
Li, MS,Li, PF,He, SP,et al. The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2002,8(3):469-475.
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