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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Okamoto, Oswaldo Keith [1] ; Carvalho, Ana Carolina S. R. [2] ; Marti, Luciana C. [2] ; Vencio, Ricardo Z. [3] ; Moreira-Filho, Carlos A. [2, 4]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurocirurgia, Sao Paulo - Brazil
[2] Inst Israelita Ensino & Pesquisa Albert Einst, Sao Paulo - Brazil
[3] Inst Syst Biol, Seattle, WA 98103 - USA
[4] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: CANCER CELL INTERNATIONAL; v. 7, 2007.
Citações Web of Science: 12
Resumo

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. (AU)

Processo FAPESP: 02/01826-5 - Controle redox de expressão gênica: caracterização de redes regulatórias e seu envolvimento na diferenciação de células-tronco (stem cells)
Beneficiário:Oswaldo Keith Okamoto
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores