A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma
A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma
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DOI：
10.1038/nm0897-917
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发表时间：
1997-08-01
期刊：
影响因子：
82.9
通讯作者：
Altieri, DC
中科院分区：
文献类型：
--
作者：
Ambrosini, G;Adida, C;Altieri, DC
程序性细胞死亡（凋亡）抑制剂异常延长细胞活力可能有助于癌症（1），促进突变的发生和促进对治疗的耐药性（2）。尽管鉴定了几种与bcl-2（2，3）或杆状病毒IAP基因（4-9）相关的新的凋亡抑制剂，但尚不清楚凋亡抑制是否在瘤形成中起普遍作用。在这里，我们描述了一个新的人类基因编码一个结构独特的IAP凋亡抑制剂，命名为生存素。Survivin含有一个单一的杆状病毒IAP重复序列，缺乏羧基末端的环指。存活素存在于胎儿发育期间，在终末分化的成人组织中检测不到。然而，存活素在体内转化的细胞系和所有最常见的人类肺癌、结肠癌、胰腺癌、前列腺癌和乳腺癌中显著表达。存活素也存在于大约50%的高级别非霍奇金淋巴瘤（中心母细胞性、免疫母细胞性）中，但不存在于低级别淋巴瘤（淋巴细胞性）中。Survivin的重组表达可抵消缺乏白细胞介素3（IL-3）的B淋巴细胞前体细胞的凋亡。这些研究结果表明，凋亡抑制可能是肿瘤的一般特征，并确定生存素作为一个潜在的新的目标，为肿瘤和淋巴瘤的治疗。
Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer(1) by facilitating the insurgence of mutations and by promoting resistance to therapy(2). Despite the identification of several new apoptosis inhibitors related to bcl-2(2,3) or to the baculovirus IAP gene(4-9), it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.