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 Brain-metastatic breast cancer ( BMBC ) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown . Recent work has demonstrated that deregulation of epidermal growth factor receptor ( EGFR ) may correlate with BMBC progression . However , the exact contribution that EGFR makes to BMBC remains unclear . METHODS The role of EGFR in BMBC was explored by serial analyses in a brain-trophic clone of human MDA-MB-231 breast carcinoma cells ( 231-BR cells ) . EGFR expression was inhibited by stable short-hairpin RNA transfection or by the kinase inhibitor erlotinib , and it was activated by heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) . Cell growth and invasion activities also were analyzed in vitro and in vivo . RESULTS EGFR inhibition or activation strongly affected 231-BR cell migration/invasion activities as assessed by an adhesion assay , a wound-healing assay , a Boyden chamber invasion assay , and cytoskeleton staining . Also , EGFR inhibition significantly decreased brain metastases of 231-BR cells in vivo . Surprisingly , changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay , an anchorage-independent growth assay , and cell cycle analysis . Immunoblot analysis suggested that EGFR drives cells ' invasiveness capability mainly through phosphoinositide 3-kinase/protein kinase B and phospholipase C Î³ downstream pathways . In addition , EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen-activated protein kinase pathway . CONCLUSIONS The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231-BR cells , providing new evidence of the potential value of EGFR inhibition in treating BMBC .
    OUTPUT:

agent
activating invasion and metastasis;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: BACKGROUND Brain-metastatic breast cancer ( BMBC ) is increasing and poses a severe clinical problem because of the lack of effective treatments and because the underlying molecular mechanisms are largely unknown . Recent work has demonstrated that deregulation of epidermal growth factor receptor ( EGFR ) may correlate with BMBC progression . However , the exact contribution that EGFR makes to BMBC remains unclear . METHODS The role of EGFR in BMBC was explored by serial analyses in a brain-trophic clone of human MDA-MB-231 breast carcinoma cells ( 231-BR cells ) . EGFR expression was inhibited by stable short-hairpin RNA transfection or by the kinase inhibitor erlotinib , and it was activated by heparin-binding epidermal growth factor-like growth factor ( HB-EGF ) . Cell growth and invasion activities also were analyzed in vitro and in vivo . RESULTS EGFR inhibition or activation strongly affected 231-BR cell migration/invasion activities as assessed by an adhesion assay , a wound-healing assay , a Boyden chamber invasion assay , and cytoskeleton staining . Also , EGFR inhibition significantly decreased brain metastases of 231-BR cells in vivo . Surprisingly , changes to EGFR expression affected cell proliferation activities less significantly as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT ) assay , an anchorage-independent growth assay , and cell cycle analysis . Immunoblot analysis suggested that EGFR drives cells ' invasiveness capability mainly through phosphoinositide 3-kinase/protein kinase B and phospholipase C Î³ downstream pathways . In addition , EGFR was involved less in proliferation because of the insensitivity of the downstream mitogen-activated protein kinase pathway . CONCLUSIONS The current results indicated that EGFR plays more important roles in cell migration and invasion to the brain than in cell proliferation progression on 231-BR cells , providing new evidence of the potential value of EGFR inhibition in treating BMBC .
    OUTPUT:
