Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4

Murn, J., Alibert, O., Wu, N., Tendil, S., Gidrol, X. (December 2008) Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4. J Exp Med, 205 (13). pp. 3091-103.

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Abstract

B cell receptor (BCR) signaling contributes to the pathogenesis of B cell malignancies, and most B cell lymphomas depend on BCR signals for survival. Identification of genes that restrain BCR-mediated proliferation is therefore an important goal toward improving the therapy of B cell lymphoma. Here, we identify Ptger4 as a negative feedback regulator of proliferation in response to BCR signals and show that its encoded EP4 receptor is a principal molecule conveying the growth-suppressive effect of prostaglandin E2 (PGE2). Stable knockdown of Ptger4 in B cell lymphoma markedly accelerated tumor spread in mice, whereas Ptger4 overexpression yielded significant protection. Mechanistically, we show that the intrinsic activity of Ptger4 and PGE2-EP4 signaling target a similar set of activating genes, and find Ptger4 to be significantly down-regulated in human B cell lymphoma. We postulate that Ptger4 functions in B cells as a candidate tumor suppressor whose activity is regulated by PGE2 in the microenvironment. These findings suggest that targeting EP4 receptor for prostaglandin may present a novel strategy for treatment of B cell malignancies.

Item Type:	Paper
Uncontrolled Keywords:	Animals B-Lymphocytes/cytology/immunology/*physiology *Cell Proliferation Dinoprostone/*metabolism Female Gene Expression Profiling Gene Expression Regulation *Genes, Tumor Suppressor Humans Lymphoma, B-Cell/genetics/metabolism Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Neoplasm Transplantation Oligonucleotide Array Sequence Analysis Receptors, Prostaglandin E/genetics/*metabolism Signal Transduction/physiology Social Control, Formal Survival Rate
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > B cells diseases & disorders > cancer diseases & disorders organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > inflammation organs, tissues, organelles, cell types and functions
CSHL Authors:	Murn, Jernej
Communities:	CSHL labs > Trotman lab
Depositing User:	Matt Covey
Date:	22 December 2008
Date Deposited:	25 Feb 2013 21:35
Last Modified:	25 Feb 2013 21:35
PMCID:	PMC2605229
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27597

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