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: The evidence that androgen blockade-resistant prostate cancer , termed castration resistant , remains androgen receptor ( AR ) dependent is compelling . AR is re-activated through multiple mechanisms including expression of constitutively active splice variants that lack hormone binding domains ( HBDs ) . This highlights need to develop therapies that target regions other than the HBD . Because the p160 coactivators interact most strongly with the amino-terminus of AR , we examined the consequences of disrupting this interaction . We identified two overlapping SRC-1 peptides that interact with AR , but not with progesterone receptor . These peptides reduce AR and AR variant AR-V7 dependent induction of an AR responsive reporter . Using mammalian two hybrid assays , we found that the peptides interrupt the AR/SRC-1 , AR/SRC-2 and AR N/C interactions , but not SRC-1/CARM-1 interactions . Consistent with the SRC-1 dependence of induced , but not repressed genes , in LNCaP cells , the peptides inhibited hormone dependent induction of endogenous target genes including PSA and TMPRSS2 , but did not block AR dependent repression of UGT2B17 or inhibit vitamin D receptor activity . Simultaneous detection of SRC-1 peptides and PSA by double immunofluorescence in transfected LNCaP cells clearly demonstrated a strong reduction in PSA levels in cells expressing the peptides . The peptides also inhibited the AR dependent expression of PSA in castration resistant C4-2 cells . Moreover they inhibited androgen dependent proliferation of LNCaP cells and proliferation of C4-2 cells in androgen depleted medium without affecting AR negative PC-3 cells . Thus , the p160 coactivator binding site is a novel potential therapeutic target to inhibit AR activity .
    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: The evidence that androgen blockade-resistant prostate cancer , termed castration resistant , remains androgen receptor ( AR ) dependent is compelling . AR is re-activated through multiple mechanisms including expression of constitutively active splice variants that lack hormone binding domains ( HBDs ) . This highlights need to develop therapies that target regions other than the HBD . Because the p160 coactivators interact most strongly with the amino-terminus of AR , we examined the consequences of disrupting this interaction . We identified two overlapping SRC-1 peptides that interact with AR , but not with progesterone receptor . These peptides reduce AR and AR variant AR-V7 dependent induction of an AR responsive reporter . Using mammalian two hybrid assays , we found that the peptides interrupt the AR/SRC-1 , AR/SRC-2 and AR N/C interactions , but not SRC-1/CARM-1 interactions . Consistent with the SRC-1 dependence of induced , but not repressed genes , in LNCaP cells , the peptides inhibited hormone dependent induction of endogenous target genes including PSA and TMPRSS2 , but did not block AR dependent repression of UGT2B17 or inhibit vitamin D receptor activity . Simultaneous detection of SRC-1 peptides and PSA by double immunofluorescence in transfected LNCaP cells clearly demonstrated a strong reduction in PSA levels in cells expressing the peptides . The peptides also inhibited the AR dependent expression of PSA in castration resistant C4-2 cells . Moreover they inhibited androgen dependent proliferation of LNCaP cells and proliferation of C4-2 cells in androgen depleted medium without affecting AR negative PC-3 cells . Thus , the p160 coactivator binding site is a novel potential therapeutic target to inhibit AR activity .
    OUTPUT:
