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Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer

BACKGROUND: Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell ex...

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Autores principales: Okamoto, Oswaldo Keith, Carvalho, Ana Carolina SR, Marti, Luciana C, Vêncio, Ricardo Z, Moreira-Filho, Carlos A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904434/
https://www.ncbi.nlm.nih.gov/pubmed/17559657
http://dx.doi.org/10.1186/1475-2867-7-11
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author Okamoto, Oswaldo Keith
Carvalho, Ana Carolina SR
Marti, Luciana C
Vêncio, Ricardo Z
Moreira-Filho, Carlos A
author_facet Okamoto, Oswaldo Keith
Carvalho, Ana Carolina SR
Marti, Luciana C
Vêncio, Ricardo Z
Moreira-Filho, Carlos A
author_sort Okamoto, Oswaldo Keith
collection PubMed
description BACKGROUND: Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. METHODS: CD34+/CD133+ progenitor cells were purified from human umbilical cord blood and expanded in vitro. Correlated molecular changes were analyzed by gene expression profiling using microarrays covering up to 55,000 transcripts. Genes regulated during progenitor cell expansion were identified and functionally classified. Aberrant expression of such genes in cancer was indicated by in silico SAGE. Differential expression of selected genes was assessed by real-time PCR in hematopoietic cells from chronic myeloid leukemia patients and healthy individuals. RESULTS: Several genes and signaling pathways not previously associated with ex vivo expansion of CD133+/CD34+ cells were identified, most of which associated with cancer. Regulation of MEK/ERK and Hedgehog signaling genes in addition to numerous proto-oncogenes was detected during conditions of enhanced progenitor cell expansion. Quantitative real-time PCR analysis confirmed down-regulation of several newly described cancer-associated genes in CD133+/CD34+ cells, including DOCK4 and SPARCL1 tumor suppressors, and parallel results were verified when comparing their expression in cells from chronic myeloid leukemia patients CONCLUSION: Our findings reveal potential molecular targets for oncogenic transformation in CD133+/CD34+ cells and strengthen the link between deregulation of stem/progenitor cell expansion and the malignant process.
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spelling pubmed-19044342007-06-30 Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer Okamoto, Oswaldo Keith Carvalho, Ana Carolina SR Marti, Luciana C Vêncio, Ricardo Z Moreira-Filho, Carlos A Cancer Cell Int Primary Research BACKGROUND: Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. METHODS: CD34+/CD133+ progenitor cells were purified from human umbilical cord blood and expanded in vitro. Correlated molecular changes were analyzed by gene expression profiling using microarrays covering up to 55,000 transcripts. Genes regulated during progenitor cell expansion were identified and functionally classified. Aberrant expression of such genes in cancer was indicated by in silico SAGE. Differential expression of selected genes was assessed by real-time PCR in hematopoietic cells from chronic myeloid leukemia patients and healthy individuals. RESULTS: Several genes and signaling pathways not previously associated with ex vivo expansion of CD133+/CD34+ cells were identified, most of which associated with cancer. Regulation of MEK/ERK and Hedgehog signaling genes in addition to numerous proto-oncogenes was detected during conditions of enhanced progenitor cell expansion. Quantitative real-time PCR analysis confirmed down-regulation of several newly described cancer-associated genes in CD133+/CD34+ cells, including DOCK4 and SPARCL1 tumor suppressors, and parallel results were verified when comparing their expression in cells from chronic myeloid leukemia patients CONCLUSION: Our findings reveal potential molecular targets for oncogenic transformation in CD133+/CD34+ cells and strengthen the link between deregulation of stem/progenitor cell expansion and the malignant process. BioMed Central 2007-06-08 /pmc/articles/PMC1904434/ /pubmed/17559657 http://dx.doi.org/10.1186/1475-2867-7-11 Text en Copyright © 2007 Okamoto 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 Primary Research
Okamoto, Oswaldo Keith
Carvalho, Ana Carolina SR
Marti, Luciana C
Vêncio, Ricardo Z
Moreira-Filho, Carlos A
Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title_full Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title_fullStr Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title_full_unstemmed Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title_short Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer
title_sort common molecular pathways involved in human cd133+/cd34+ progenitor cell expansion and cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904434/
https://www.ncbi.nlm.nih.gov/pubmed/17559657
http://dx.doi.org/10.1186/1475-2867-7-11
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