Absence of the steroid receptor coactivator-3 induces B-cell lymphoma
Absence of the steroid receptor coactivator-3 induces B-cell lymphoma
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DOI：
10.1038/sj.emboj.7601106
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发表时间：
2006-06-07
期刊：
影响因子：
11.4
通讯作者：
Auwerx, Johan
中科院分区：
文献类型：
--
作者：
Coste, Agnes;Antal, Maria Cristina;Auwerx, Johan
类固醇受体辅激活因子3（SRC-3/ACTR/AIB-1/pCIP/RAC 3/TRAM-1）是核受体辅激活因子p160家族的成员，在乳腺生长、发育和肿瘤发生中起重要作用。我们发现SRC-3基因的缺失减少了血小板，增加了淋巴细胞的数量，导致恶性B细胞淋巴瘤的发展。SRC-3（-/-）小鼠淋巴系的扩增是细胞自主的，与继发于组成性NF-κ B活化的增殖和抗凋亡基因的诱导相关，并且可以通过恢复SRC-3表达来逆转。NF-κ B活化通过I κ B降解来解释，其结果是游离I κ B激酶增加，其不再被SRC-3抑制。这些结果表明，SRC-3调节淋巴细胞生成，并且与先前的研究相结合表明，SRC-3对细胞增殖具有极大不同的影响，这取决于细胞环境，范围从增殖和致瘤（乳腺）到抗增殖（淋巴细胞）作用。
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-kappa B activation, and can be reversed by restoration of SRC-3 expression. NF-kappa B activation is explained by the degradation of I kappa B, consequent to increases in free I kappa 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.