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Papers In Press, published online ahead of print March 14, 2005
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens 115 22
Corresponding Author: perez{at}ciic.gr
CRD-BP/IMP1 is an RNA binding protein recognizing specifically c-myc, leader 3’ IGF-II and tau mRNAs and the H19 RNA. CRD-BP/IMP1 is predominantly expressed in embryonal tissues, but is de novo activated and/or overexpressed in various human neoplasias. To address the question whether CRD-BP/IMP1 expression characterizes certain cell types, displaying distinct proliferation and/or differentiation properties (i.e. stem cells), we isolated cell subpopulations from human bone marrow, mobilized peripheral blood, and cord blood, all sources known to contain stem cells, and monitored for its expression. CRD-BP/IMP1 was detected only in cord blood derived CD34+ stem cells and not in any other cell type of either adult or cord blood origin. Adult BM CD34+ cells cultured in the presence of 5’-azacytidine expressed de novo CRD-BP/IMP1, suggesting that epigenetic modifications may be responsible for its silencing in adult non-expressing cells. Furthermore, by applying the siRNA methodology in MCF-7 cells we observed, subsequent to knocking down of CRD-BP/IMP1, decreased c-myc expression, increased IGF-II mRNA levels and reduced cell proliferation rates. These data: 1) suggest a normal role for CRD-BP/IMP1 in pluripotent stem cells with high renewal capacity, like the CB CD34+ cells; 2) indicate that altered methylation may directly or indirectly affect its expression in adult cells; 3) imply that its de novo activation in cancer cells, may affect the expression of c-Myc and IGF-II, and 4) indicate that the inhibition of CRD-BP/IMP1 expression might affect cancer cell proliferation.
J. Biol. Chem, 10.1074/jbc.M410036200
Submitted on September 1, 2004
Revised on March 11, 2005
Accepted on March 13, 2005
CRD-BP/IMP1 expression characterizes cord blood CD34+ stem cells and affects c-myc and IGF-II expression in MCF-7 cancer cells
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