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: BACKGROUND Prostate cancer ( PCa ) progression is often associated with transactivation of the androgen receptor ( AR ) by endogenous hormones/growth factors . One such factor affecting growth , proliferation , and apoptostis ( pro-/anti- ) in various cancers is the adipokine leptin . This research studied leptin-induced signaling and apoptosis in androgen sensitive ( LNCaP , PC3/AR ) and insensitive ( PC3 , DU145 ) PCa cell lines . METHODS Signaling was studied by immunoblotting in cells overexpressing leptin receptors ( LRb ) , Janus kinase 2 ( JAK2 ) , and kinase negative-HER2-YFP cDNAs . Apoptosis was measured by immunoblotting of apoptotic proteins and by Hoechst staining of condensed DNA . RESULTS Leptin rapidly induced activation of JAK2 , STAT3 , and MAPK ( ERK1/2 ) signaling cascades ; it may also induce HER2 transactivation via leptin-induced phospho-JAK2 . Leptin was then shown to exert clear pro-apoptotic effects , increasing levels of caspase 3 , cleavage of its substrate , poly ( ADP-ribose ) polymerase ( PARP ) to cleaved PARP(89) , levels of CK 18 , a cytoskeletal protein formed during apoptosis , and DNA condensation . Kinase inhibitors indicated that leptin-induced apoptosis is probably mediated by balanced activation of JAK2/STAT3 , p38 MAPK , and PKC pathways in PCa cells . A human leptin mutein LRb antagonist , L39A/D40A/F41A , fully inhibited leptin-induced phosphorylation of JAK2 , ERK1/2 , and Akt/PKB , and partially abrogated effects on apoptotic proteins . In LNCaP and PC3/AR cells , leptin increased AR protein levels in correlation with raised apoptotic markers . Thus , AR may mediate , at least partly , the leptin-induced apoptotic response . CONCLUSIONS Leptin can clearly induce apoptosis in human PCa cell lines . These findings could lead to development of new leptin agonists with enhanced pro-apoptotic effects and targeted for use in human PCa .
    OUTPUT:

agent
sustaining proliferative signaling;resisting cell death
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: BACKGROUND Prostate cancer ( PCa ) progression is often associated with transactivation of the androgen receptor ( AR ) by endogenous hormones/growth factors . One such factor affecting growth , proliferation , and apoptostis ( pro-/anti- ) in various cancers is the adipokine leptin . This research studied leptin-induced signaling and apoptosis in androgen sensitive ( LNCaP , PC3/AR ) and insensitive ( PC3 , DU145 ) PCa cell lines . METHODS Signaling was studied by immunoblotting in cells overexpressing leptin receptors ( LRb ) , Janus kinase 2 ( JAK2 ) , and kinase negative-HER2-YFP cDNAs . Apoptosis was measured by immunoblotting of apoptotic proteins and by Hoechst staining of condensed DNA . RESULTS Leptin rapidly induced activation of JAK2 , STAT3 , and MAPK ( ERK1/2 ) signaling cascades ; it may also induce HER2 transactivation via leptin-induced phospho-JAK2 . Leptin was then shown to exert clear pro-apoptotic effects , increasing levels of caspase 3 , cleavage of its substrate , poly ( ADP-ribose ) polymerase ( PARP ) to cleaved PARP(89) , levels of CK 18 , a cytoskeletal protein formed during apoptosis , and DNA condensation . Kinase inhibitors indicated that leptin-induced apoptosis is probably mediated by balanced activation of JAK2/STAT3 , p38 MAPK , and PKC pathways in PCa cells . A human leptin mutein LRb antagonist , L39A/D40A/F41A , fully inhibited leptin-induced phosphorylation of JAK2 , ERK1/2 , and Akt/PKB , and partially abrogated effects on apoptotic proteins . In LNCaP and PC3/AR cells , leptin increased AR protein levels in correlation with raised apoptotic markers . Thus , AR may mediate , at least partly , the leptin-induced apoptotic response . CONCLUSIONS Leptin can clearly induce apoptosis in human PCa cell lines . These findings could lead to development of new leptin agonists with enhanced pro-apoptotic effects and targeted for use in human PCa .
    OUTPUT:
