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: To examine the association of cell cycle regulatory gene inactivation with human cell immortalization , we determined the expression status of INK4a , Rb , and WAF1/ CIP1 , in eleven in vitro immortalized human cell lines , including fibroblasts and keratinocytes . Two human papillomavirus type 16 E6 expressing cell lines with telomerase activity , including a fibroblast cell line and a keratinocyte cell line , expressed no detectable p16(INK4a) . These cell lines had a hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1) . All of seven fibroblast cell lines immortalized either spontaneously or by ( 60)Co , X-rays , 4-nitroquinoline 1-oxide or aflatoxin B(1) , maintaining their telomeres by the ALT ( alternative lengthening of telomeres ) pathway , displayed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . Levels of p21(WAF1/CIP1) expression varied among the cell lines . Two fibroblast cell lines that became immortalized following infection with a retrovirus vector encoding human telomerase catalytic subunit ( hTERT ) cDNA were also accompanied by inactivation of p16(INK4a) and pRb pathways . Acquisition of telomerase activity alone was not sufficient for immortalization of these cell lines . Taken together , all the cell lines including fibroblasts and keratinocytes , with either telomerase activity or the ALT pathway for telomere maintenance showed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . These demonstrate the association of inactivation of both p16(INK4a) and pRb with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells .
    OUTPUT:

agent
enabling replicative immortality
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.
    ###
    INPUT: To examine the association of cell cycle regulatory gene inactivation with human cell immortalization , we determined the expression status of INK4a , Rb , and WAF1/ CIP1 , in eleven in vitro immortalized human cell lines , including fibroblasts and keratinocytes . Two human papillomavirus type 16 E6 expressing cell lines with telomerase activity , including a fibroblast cell line and a keratinocyte cell line , expressed no detectable p16(INK4a) . These cell lines had a hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1) . All of seven fibroblast cell lines immortalized either spontaneously or by ( 60)Co , X-rays , 4-nitroquinoline 1-oxide or aflatoxin B(1) , maintaining their telomeres by the ALT ( alternative lengthening of telomeres ) pathway , displayed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . Levels of p21(WAF1/CIP1) expression varied among the cell lines . Two fibroblast cell lines that became immortalized following infection with a retrovirus vector encoding human telomerase catalytic subunit ( hTERT ) cDNA were also accompanied by inactivation of p16(INK4a) and pRb pathways . Acquisition of telomerase activity alone was not sufficient for immortalization of these cell lines . Taken together , all the cell lines including fibroblasts and keratinocytes , with either telomerase activity or the ALT pathway for telomere maintenance showed loss of expression of p16(INK4a) and hyperphosphorylation of pRb . These demonstrate the association of inactivation of both p16(INK4a) and pRb with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells .
    OUTPUT:
