title: Absence of the steroid receptor coactivator-3 induces B-cell lymphoma.
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-kappaB activation, and can be reversed by restoration of SRC-3 expression. NF-kappaB activation is explained by the degradation of IkappaB, consequent to increases in free IkappaB 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.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, Illkirch, France.
authors: Agnès
authors: A
authors: Coste
authors: Maria Cristina
authors: MC
authors: Antal
authors: Susan
authors: S
authors: Chan
authors: Philippe
authors: P
authors: Kastner
authors: Manuel
authors: M
authors: Mark
authors: Bert W
authors: BW
authors: O'Malley
authors: Johan
authors: J
authors: Auwerx