Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4
| Autor: | Xavier Gidrol, Olivier Alibert, Ning Wu, Jernej Murn, Simon Tendil |
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| Rok vydání: | 2008 |
| Předmět: |
CD30
Lymphoma Formal Inbred C57BL Medical and Health Sciences Mice hemic and lymphatic diseases Receptors Immunology and Allergy 2.1 Biological and endogenous factors Genes Tumor Suppressor Aetiology B-cell lymphoma Receptor Inbred BALB C Oligonucleotide Array Sequence Analysis Cancer Mice Knockout Mice Inbred BALB C B-Lymphocytes Social Control Prostaglandin E Articles Hematology Survival Rate medicine.anatomical_structure lipids (amino acids peptides and proteins) Female Signal transduction Tumor Suppressor Signal Transduction Biotechnology Lymphoma B-Cell Knockout B-cell receptor Immunology EP4 Receptor Biology Article Dinoprostone Rare Diseases Clinical Research medicine Receptors Prostaglandin E Animals Humans B cell Cell Proliferation Cell growth Gene Expression Profiling B-Cell medicine.disease Molecular biology Social Control Formal Mice Inbred C57BL Gene Expression Regulation Genes Cancer research EP4 Subtype Receptors Prostaglandin E EP4 Subtype Neoplasm Transplantation |
| Zdroj: | The Journal of experimental medicine, vol 205, iss 13 The Journal of Experimental Medicine |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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