Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas

Oncogene
Agustín SánchezJosé M Rojas

Abstract

Spry2 has been characterized as a negative regulator of the extracellular-regulated kinase (ERK) pathway. In this study we analysed whether epigenetic alterations of hSpry2 promoter occur in human lymphoid/hematopoietic malignancies. Our results revealed that hSpry2 promoter was hypermethylated in the HT cell line derived from a B-cell diffuse lymphoma, which correlated with decreased hSpry2 expression. We detected deregulation of the ERK pathway in these cells, but not in other blood cell lines expressing hSpry2. In addition, the ectopic overexpression of hSpry2 in HT cells drastically reduced the activation of ERK upon phorbol 12-myristate-13-acetate stimulation. Nude mice inoculated with HT mock cells developed tumors seven times larger than those from HT-hSpry2-transfected cells. We found hypermethylation of hSpry2 promoter in 37% (26 cases out of 71) of primary tumors from patients with B-cell diffuse lymphoma but none in normal B lymphocytes from 37 healthy individuals. Finally, we detected that hSpry2 promoter hypermethylation was associated with a significant decrease in the 5-year survival rate. These data suggest that hSpry2 could be important in lymphoid malignancies.

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Citations

Jul 26, 2013·Nature Reviews. Immunology·Robert C Rickert
Dec 20, 2012·Journal of Oncology·Samar Masoumi MoghaddamDavid Lawson Morris
Apr 20, 2014·Cancer Metastasis Reviews·Samar Masoumi-MoghaddamDavid Lawson Morris
Jan 30, 2015·International Journal of Cancer. Journal International Du Cancer·Samar Masoumi-MoghaddamDavid L Morris
Dec 19, 2009·Neuropharmacology·Herbert E CovingtonEric J Nestler
Feb 25, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zijie WangMin Gu
May 29, 2019·PLoS Computational Biology·David A KnowlesSylvia Plevritis
Sep 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yueqin ZhuYan Huang

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