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Expression profile of CREB knockdown in myeloid leukemia cells

BACKGROUND: The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells...

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Autores principales: Pellegrini, Matteo, Cheng, Jerry C, Voutila, Jon, Judelson, Dejah, Taylor, Julie, Nelson, Stanley F, Sakamoto, Kathleen M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647550/
https://www.ncbi.nlm.nih.gov/pubmed/18801183
http://dx.doi.org/10.1186/1471-2407-8-264
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author Pellegrini, Matteo
Cheng, Jerry C
Voutila, Jon
Judelson, Dejah
Taylor, Julie
Nelson, Stanley F
Sakamoto, Kathleen M
author_facet Pellegrini, Matteo
Cheng, Jerry C
Voutila, Jon
Judelson, Dejah
Taylor, Julie
Nelson, Stanley F
Sakamoto, Kathleen M
author_sort Pellegrini, Matteo
collection PubMed
description BACKGROUND: The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution. METHODS: To understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA. RESULTS: By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA. CONCLUSION: We have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle.
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spelling pubmed-26475502009-02-25 Expression profile of CREB knockdown in myeloid leukemia cells Pellegrini, Matteo Cheng, Jerry C Voutila, Jon Judelson, Dejah Taylor, Julie Nelson, Stanley F Sakamoto, Kathleen M BMC Cancer Research Article BACKGROUND: The cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution. METHODS: To understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA. RESULTS: By combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA. CONCLUSION: We have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle. BioMed Central 2008-09-18 /pmc/articles/PMC2647550/ /pubmed/18801183 http://dx.doi.org/10.1186/1471-2407-8-264 Text en Copyright © 2008 Pellegrini et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pellegrini, Matteo
Cheng, Jerry C
Voutila, Jon
Judelson, Dejah
Taylor, Julie
Nelson, Stanley F
Sakamoto, Kathleen M
Expression profile of CREB knockdown in myeloid leukemia cells
title Expression profile of CREB knockdown in myeloid leukemia cells
title_full Expression profile of CREB knockdown in myeloid leukemia cells
title_fullStr Expression profile of CREB knockdown in myeloid leukemia cells
title_full_unstemmed Expression profile of CREB knockdown in myeloid leukemia cells
title_short Expression profile of CREB knockdown in myeloid leukemia cells
title_sort expression profile of creb knockdown in myeloid leukemia cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647550/
https://www.ncbi.nlm.nih.gov/pubmed/18801183
http://dx.doi.org/10.1186/1471-2407-8-264
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