Life Sciences Division

Lymphoma: new tumour-suppressor gene discovered

CEA

Scientists at the Institute of cellular and molecular radiation biology (CEA/iRCM) have identified a new tumor-suppressor gene that plays a pivotal role in controlling the proliferation of B cells. This finding opens up new perspectives for understanding and controlling the abnormal proliferation of B cells in certain lymphomas. These results have just been published online in the 15 December issue of the Journal of Experimental Medicine.

Although great strides have been made in the therapeutic arsenal for the treatment of cancer (chemotherapy, radiotherapy, antibody-based therapy), B-cell lymphomas still do not respond well to the treatment strategies available. B cells are immune system cells whose primary function is to respond to attacks on the organism by producing antibodies. When the immune response is triggered, it causes a proliferation of certain B cells in the lymph nodes in order to produce a sufficient quantity of antibodies. This proliferation is normally tightly regulated in order to ensure an immune-system adapted response, but if allowed to continue unfettered it can lead to the development of lymphoma.

Researchers at the CEA/iRCM have just identified a new tumour-suppressor gene, Ptger4, which is necessary but also sufficient to prevent excessive lymphocytic proliferation. This gene produces a receptor protein for prostaglandins, which are inflammatory molecules known to suppress lymphocyte proliferation. This study enabled the research team to demonstrate that knocking out Ptger4 led to accelerated lymphoma spread in mice, whereas overexpression of the gene was sufficient to prevent the lymphocytes from proliferating. The researchers also observed that this gene is suppressed in lymphoma patients, thus confirming the potential role of Ptger4 in tumour development.

Caption: Localization of the prostaglandin receptor (green)
in antigen-challenged B cells.
© CEA 

Although a therapy specifically targeting the expression of this gene is still at pre-drawing board stage, these results do open up perspectives for research designed to generate deeper insight into the origins of certain lymphomas and the mechanisms underlying abnormal B-cell proliferation. These findings represent a step forward towards improved B-cell lymphoma treatment strategies.

Reference:

Jernej Murn, Olivier Alibert, Ning Wu, Simon Tendil, Xavier Gidrol. Prostaglandin E2 regulates B-cell proliferation through a candidate tumor suppressor, Ptger4. J. Exp. Med. online the 15th of december 2008.

CEA Teams:

Laboratoire d'Exploration Fonctionnelle des Génomes, Institut de Radiobiologie cellulaire et moléculaire, CEA, Evry 91057,