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 Ras association domain family 1 isoform A ( RASSF1A ) is a tumor suppressor whose inactivation is implicated in the development of many human cancers , including breast carcinomas . Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors . Here , we show that RASSF1A inhibits breast cancer growth in vivo , and suppresses estrogen receptor ( ERÎ± ) expression and function . Reconstitution of RASSF1A in MCF7 cells led to decreased ERÎ± levels and reduced sensitivity to estrogen ( E2 ) . Concomitantly , we observed decreased expression of Id1 as well as the E2-responsive genes Bcl-2 and c-Myc that cooperatively contribute to the immortalization and transformation of breast epithelial cells . This downregulation was associated with induction of cell-cycle arrest and senescence that constitute early barriers to cancer initiation and progression . Knockdown of ERÎ± showed that downregulation of ERÎ± suffices to increase senescence and inhibit expression of Bcl-2 , c-Myc and Id1 . However , enforced expression of ERÎ± only partially rescued RASSF1A-mediated growth inhibition and senescence , suggesting that suppression of ERÎ± expression and activity is not the only mechanism by which RASSF1A inhibits growth and survival of breast cancer cells . Ectopic expression of Bcl-2 , c-Myc and Id1 had little or no effect on RASSF1A-mediated growth arrest , indicating that RASSF1A acts dominantly over these oncogenes . Mechanistically , RASSF1A was found to suppress ERÎ± expression through Akt1 . It also transiently inhibited ERÎ±-induced Ras-MAPK activity after exposure of cells to E2 . Together , our data show that RASSF1A acts as a tumor suppressor in ERÎ±+ mammary epithelial cells , in part through inhibiting ERÎ± expression and activity . These findings suggest that RASSF1A has a key role in suppressing the transformation of human breast epithelial cells and ERÎ±+ breast cancer initiation .
    OUTPUT:

agent
sustaining proliferative signaling;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.
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    INPUT: The Ras association domain family 1 isoform A ( RASSF1A ) is a tumor suppressor whose inactivation is implicated in the development of many human cancers , including breast carcinomas . Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors . Here , we show that RASSF1A inhibits breast cancer growth in vivo , and suppresses estrogen receptor ( ERÎ± ) expression and function . Reconstitution of RASSF1A in MCF7 cells led to decreased ERÎ± levels and reduced sensitivity to estrogen ( E2 ) . Concomitantly , we observed decreased expression of Id1 as well as the E2-responsive genes Bcl-2 and c-Myc that cooperatively contribute to the immortalization and transformation of breast epithelial cells . This downregulation was associated with induction of cell-cycle arrest and senescence that constitute early barriers to cancer initiation and progression . Knockdown of ERÎ± showed that downregulation of ERÎ± suffices to increase senescence and inhibit expression of Bcl-2 , c-Myc and Id1 . However , enforced expression of ERÎ± only partially rescued RASSF1A-mediated growth inhibition and senescence , suggesting that suppression of ERÎ± expression and activity is not the only mechanism by which RASSF1A inhibits growth and survival of breast cancer cells . Ectopic expression of Bcl-2 , c-Myc and Id1 had little or no effect on RASSF1A-mediated growth arrest , indicating that RASSF1A acts dominantly over these oncogenes . Mechanistically , RASSF1A was found to suppress ERÎ± expression through Akt1 . It also transiently inhibited ERÎ±-induced Ras-MAPK activity after exposure of cells to E2 . Together , our data show that RASSF1A acts as a tumor suppressor in ERÎ±+ mammary epithelial cells , in part through inhibiting ERÎ± expression and activity . These findings suggest that RASSF1A has a key role in suppressing the transformation of human breast epithelial cells and ERÎ±+ breast cancer initiation .
    OUTPUT:
