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Phosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene

Oncogene volume 25, pages 1420–1423 (2006)Cite this article

Abstract

The erythroleukemia developed by spi-1/PU.1 transgenic mice is a multistep process. At disease onset, preleukemic cells are arrested in differentiation at the proerythroblast stage (HS1 stage) and their survival and growth are under the tight control of erythropoietin (Epo). During disease progression, malignant proerythroblasts characterized by Epo autonomous growth and in vivo tumorigenicity can be isolated (HS2 stage). During analysis of transcriptional profiling representive of discrete stages of leukemic progression, we found that the phosphatidylinositol 4-phosphatase type II gene was turned off in malignant cells. PI-4-phosphatase II is an enzyme that hydrolyses the 4-phosphate position of phosphatidylinositol-3-4-bisphosphate (PtdIns(3,4)P2) to form PtdIns(3)P. Using malignant cells engineered to stably express PI-4-phosphatase II, we showed that PI-4-phosphatase II reduced Akt activation level. Moreover, stimulation of malignant cells with Epo-induced PI-4-phosphatase II transcription pointing this gene as an Epo-responsive gene. This study provides first insight for a physiological role of PI-4-phosphatase II in the proerythroblast by controlling Epo responsiveness through a negative regulation of the PI3K/Akt pathway.

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Acknowledgements

The authors thank Cilag (Levallois-Perret, France) for the gift of recombinant human Epo. We are grateful to C Guillouf and R Monni for many helpful discussions and F Wendling for her comments on the manuscript. We thank P Mayeux, (Institut Cochin, Paris) for the gift of anti-p85 antibodies and B Payrastre for valuable suggestions. This work was supported by grants from the Institut National de la Santé Et de la Recherche Médicale, the Association pour la Recherche sur la Cancer, the Fondation de France, the Ligue Nationale contre le Cancer and the Institut Curie (Paris).

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  1. S Barnache and E Le Scolan: These two authors contributed equally to this work.

Authors and Affiliations

  1. Inserm U528, Institut Curie, Paris, France

    S Barnache, E Le Scolan, O Kosmider, N Denis & F Moreau-Gachelin

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  1. S Barnache
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  2. E Le Scolan
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Correspondence to F Moreau-Gachelin.

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Barnache, S., Le Scolan, E., Kosmider, O. et al. Phosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene. Oncogene 25, 1420–1423 (2006). https://doi.org/10.1038/sj.onc.1209187

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