Modulation of retinoblastoma gene in normal adult hematopoiesis: Peak expression and functional role in advanced erythroid differentiation

G. L. Condorelli, U. Testa, M. Valtieri, L. Vitelli, A. De Luca, T. Barberi, E. Montesoro, S. Campisi, A. Giordano, C. Peschle

Research output: Contribution to journalArticle

Abstract

The retinoblastoma (RB) gene specifies a nuclear phosphoprotein (pRb 105), which is a prototype tumor suppressor inactivated in a variety of human tumors. Recent studies suggest that RB is also involved in embryonic development of murine central nervous and hematopoietic systems. We have investigated RB expression and function in human adult hematopoiesis-i.e., in liquid suspension culture of purified quiescent hematopoietic progenitor cells (HPCs) induced by growth factor stimulus to proliferation and unilineage differentiation/maturation through the erythroid or granulocytic lineage. In the initial HPC differentiation stages, the RB gene is gradually induced at the mRNA and protein level in both erythroid and granulopoietic cultures. In late HPC differentiation and then precursor maturation, RB gene expression is sustained in the erythroid lineage, whereas it is sharply downmodulated in the granulocytic series. Functional studies were performed by treatment of HPC differentiation culture with phosphorothioate antisense oligomer targeting Rb mRNA; coherent with the expression pattern, oligomer treatment of late HPCs causes a dose-dependent and selective inhibition of erythroid colony formation. These observations suggest that the RB gene plays an erythroid- and stage-specific functional role in normal adult hematopoiesis, particularly at the level of late erythroid HPCs.

Original languageEnglish
Pages (from-to)4808-4812
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number11
DOIs
Publication statusPublished - May 23 1995

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Retinoblastoma Genes
Hematopoiesis
Hematopoietic Stem Cells
Cell Differentiation
Retinoblastoma
Hematopoietic System
Messenger RNA
Erythroid Precursor Cells
Phosphoproteins
Embryonic Development
Neoplasms
Intercellular Signaling Peptides and Proteins
Suspensions
Central Nervous System
Cell Culture Techniques
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

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Modulation of retinoblastoma gene in normal adult hematopoiesis : Peak expression and functional role in advanced erythroid differentiation. / Condorelli, G. L.; Testa, U.; Valtieri, M.; Vitelli, L.; De Luca, A.; Barberi, T.; Montesoro, E.; Campisi, S.; Giordano, A.; Peschle, C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 11, 23.05.1995, p. 4808-4812.

Research output: Contribution to journalArticle

Condorelli, G. L. ; Testa, U. ; Valtieri, M. ; Vitelli, L. ; De Luca, A. ; Barberi, T. ; Montesoro, E. ; Campisi, S. ; Giordano, A. ; Peschle, C. / Modulation of retinoblastoma gene in normal adult hematopoiesis : Peak expression and functional role in advanced erythroid differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 11. pp. 4808-4812.
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