Article
- The EMBO Journal (2006) 25, 2453 - 2464
- doi:10.1038/sj.emboj.7601106
Published online: 4 May 2006
Subject Categories:
Absence of the steroid receptor coactivator-3 induces B-cell lymphoma
Agnès Coste1, Maria Cristina Antal2, Susan Chan1, Philippe Kastner1,2, Manuel Mark1,2, Bert W O'malley3 and Johan Auwerx1,2
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, Illkirch, France
- Institut Clinique de la Souris, Génopole Strasbourg, Illkirch, France
- Department of Molecular and Cellular Biology, Baylor College of Medecine, Houston, TX, USA
Correspondence to:
Johan Auwerx, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Parc d'Innovation, 1 rue Laurent Fries, BP10142, 67404 Illkirch, France. Tel.: +33 388 653425; Fax: +33 388 653201; E-mail: auwerx@igbmc.u-strasbg.fr
Received 24 November 2005; Accepted 29 March 2006
Abstract
Steroid receptor coactivator 3 (SRC-3/ACTR/AIB-1/pCIP/RAC3/TRAM-1) is a member of the p160 family of nuclear receptor coactivators that plays an important role in mammary gland growth, development, and tumorigenesis. We show that deletion of SRC-3 gene decreases platelet and increases lymphocytes numbers, leading to the development of malignant B-cell lymphomas upon aging. The expansion of the lymphoid lineage in SRC-3-/- mice is cell autonomous, correlates with an induction of proliferative and antiapoptotic genes secondary to constitutive NF-
B activation, and can be reversed by restoration of SRC-3 expression. NF-
B activation is explained by the degradation of I
B, consequent to increases in free I
B kinase, which is no longer inhibited by SRC-3. These results demonstrate that SRC-3 regulates lymphopoiesis and in combination with previous studies indicate that SRC-3 has vastly diverging effects on cell proliferation depending on the cellular context, ranging from proliferative and tumorigenic (breast) to antiproliferative (lymphoid cells) effects.
Keywords:
- cofactors,
- hematopoiesis,
- lymphoma,
- NF-
B, - transcription
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