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Titolo:
Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis
Autore:
von Lindern, M; Deiner, EM; Dolznig, H; Parren-van Amelsvoort, M; Hayman, MJ; Mullner, EW; Beug, H;
Indirizzi:
Inst Mol Pathol, A-1030 Vienna, Austria Inst Mol Pathol Vienna Austria A-1030 Mol Pathol, A-1030 Vienna, Austria Erasmus Med Ctr Rotterdam, Inst Hematol, NL-3000 DR Rotterdam, NetherlandsErasmus Med Ctr Rotterdam Rotterdam Netherlands NL-3000 DR , Netherlands Vienna Bioctr, VBC, Inst Med Biochem, A-1030 Vienna, Austria Vienna Bioctr Vienna Austria A-1030 Med Biochem, A-1030 Vienna, Austria SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook Stony Brook NY USA 11794 biol, Stony Brook, NY 11794 USA
Titolo Testata:
ONCOGENE
fascicolo: 28, volume: 20, anno: 2001,
pagine: 3651 - 3664
SICI:
0950-9232(20010621)20:28<3651:LTONME>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEM-CELL-FACTOR; GROWTH-FACTOR RECEPTOR; SELF-RENEWAL; HEMATOPOIETIC-CELLS; GLUCOCORTICOID RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TERMINAL DIFFERENTIATION; TRANSCRIPTION FACTOR; TYROSINE KINASE; IN-VITRO;
Keywords:
erythropoiesis; signal transduction; cellular transformation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Beug, H Inst Mol Pathol, Dr Bohrgasse 7, A-1030 Vienna, Austria Inst Mol Pathol Dr Bohrgasse 7 Vienna Austria A-1030 nna, Austria
Citazione:
M. von Lindern et al., "Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis", ONCOGENE, 20(28), 2001, pp. 3651-3664

Abstract

Primary erythroid progenitors can be expanded by the synergistic action oferythropoietin (Epo), stem cell factor (SCF) and glucocorticoids, While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainlycontribute to stress erythropoiesis in hypoxic mice, This ability of normal erythroid progenitors to undergo expansion under stress conditions is targeted by the avian erythroblastosis virus (AEV), harboring the oncogenes v-ErbB and v-ErbA, We investigated the signaling pathways required for progenitor expansion under stress conditions and in leukemic transformation. Immortal strains of erythroid progenitors, able to undergo normal, terminal differentiation under appropriate conditions, were established from fetal livers of p53-/- mice. Expression and activation of the EGF-receptor (HER-1/c-ErbB) or its mutated oncogenic version (v-ErbB) in these cells abrogated therequirement for Epo and SCF in expansion of these progenitors and blocked terminal differentiation. Upon inhibition of ErbB function, differentiationinto erythrocytes occurred. Signal transducing molecules important for renewal induction, i.e. Stat5- and phosphoinositide 3-kinase (PI3K), are utilized by both EpoR/c-Kit and v/c-ErbB, However, while v-ErbB transformed cells and normal progenitors depended on PI3K signaling for renewal, c-ErbB also induces progenitor expansion by PI3K-independent mechanisms.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 03:39:32