| First Author | Coste A | Year | 2006 |
| Journal | EMBO J | Volume | 25 |
| Issue | 11 | Pages | 2453-64 |
| PubMed ID | 16675958 | Mgi Jnum | J:109522 |
| Mgi Id | MGI:3629241 | Doi | 10.1038/sj.emboj.7601106 |
| Citation | Coste A, et al. (2006) Absence of the steroid receptor coactivator-3 induces B-cell lymphoma. EMBO J 25(11):2453-64 |
| abstractText | 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. |
