human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: 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 , 3H-thymidine incorporation and S-stage percentage of cell cycle analysis . With radioactive labeled 125I-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 , p 53 , 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 , ( 3)H-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 x10(-8)mol . ( -1)L 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(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells . In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control . CONCLUSION These results demonstrate that AFP is a 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 .
    OUTPUT:

agent
sustaining proliferative signaling
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: 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 , 3H-thymidine incorporation and S-stage percentage of cell cycle analysis . With radioactive labeled 125I-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 , p 53 , 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 , ( 3)H-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 x10(-8)mol . ( -1)L 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(20mg.L(-1)) could upregulate the expression of N- ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells . In the later case,the alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control . CONCLUSION These results demonstrate that AFP is a 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 .
    OUTPUT:
