Newton Ryan H, Lu Yu, Papa Antonella, Whitcher Greg H, Kang Youn-Jung, Yan Catherine, Pandolfi Pier Paolo, Turka Laurence A
Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital.
Department of Medicine, Brigham and Women's Hospital.
Blood. 2015 Jan 29;125(5):852-5. doi: 10.1182/blood-2014-04-571372. Epub 2014 Dec 4.
Mice with T-cell-specific loss of the tumor suppressor gene PTEN early in T-cell ontogeny develop thymic lymphomas that invariably harbor a reciprocal translocation involving the T-cell receptor α/δ locus and c-myc, t(14;15). In addition to its known function as a lipid phosphatase opposing PI3K signaling, PTEN has also been described as playing a prominent role in promoting genomic stability. As a result, it has been uncertain which one(s) of these 2 separable features were required to block the development of lymphoma. Here, using a conditional model in which T cells selectively express 1 phosphatase-dead PTEN mutant (C124S) and maintain 1 null allele, we show that PTEN phosphatase activity is required for preventing the emergence of a malignant T-cell population harboring t(14;15), thus constituting a critical function of PTEN in preventing lymphomagenesis.
在T细胞发育早期肿瘤抑制基因PTEN发生T细胞特异性缺失的小鼠会发生胸腺淋巴瘤，这些淋巴瘤总是含有涉及T细胞受体α/δ基因座和c-myc的相互易位，即t(14;15)。除了其作为对抗PI3K信号传导的脂质磷酸酶的已知功能外，PTEN还被描述为在促进基因组稳定性方面发挥重要作用。因此，尚不清楚这两个可分离的特征中哪一个是阻止淋巴瘤发生所必需的。在这里，我们使用一种条件模型，其中T细胞选择性表达1种磷酸酶失活的PTEN突变体（C124S）并维持1个无效等位基因，结果表明PTEN磷酸酶活性是防止携带t(14;15)的恶性T细胞群体出现所必需的，因此这构成了PTEN在预防淋巴瘤发生中的关键功能。
