Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation.
Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation.
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发表时间：
1998
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通讯作者：
C. Adida;Paul L. Crotty;James;McGrath;D. Berrebi;J. Diebold;D. Altieri
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作者：
C. Adida;Paul L. Crotty;James;McGrath;D. Berrebi;J. Diebold;D. Altieri
程序性细胞死亡（凋亡）的抑制剂可以调节组织分化，并异常促进瘤形成中的细胞存活。IAP基因家族的一种新的凋亡抑制剂，命名为生存素，最近被发现在所有最常见的人类癌症，但不是在正常的，终末分化的成人组织。探讨Survivin在胚胎及胎儿发育过程中的表达。免疫组织化学和原位杂交研究表明，在几个凋亡调控的胎儿组织，包括复层上皮干细胞层，内分泌胰腺，胸腺髓质，与另一种凋亡抑制剂，bcl-2的模式不重叠的生存素的强表达。一个序列特异性抗体的生存素免疫印迹一个单一的约16.5 kd的生存素带在人胎儿肺，肝，心脏，肾，胃肠道。在小鼠胚胎中，在胚胎第11.5天（E）发现了显著且几乎无处不在的生存素分布，而在E15至E21，生存素表达仅限于肺的远端细支气管上皮和神经嵴衍生的细胞，包括背根神经节神经元、垂体和脉络丛。这些数据表明，生存素在胚胎和胎儿发育中的表达可能有助于独立于bcl-2的组织稳态和分化。这种发育途径的畸变可能导致肿瘤中生存素的显著再表达和异常延长的细胞活力。
Inhibitors of programmed cell death (apoptosis) may regulate tissue differentiation and aberrantly promote cell survival in neoplasia. A novel apoptosis inhibitor of the IAP gene family, designated survivin, was recently found in all of the most common human cancers but not in normal, terminally differentiated adult tissues. The expression of survivin in embryonic and fetal development was investigated. Immunohistochemistry and in situ hybridization studies demonstrated strong expression of survivin in several apoptosis-regulated fetal tissues, including the stem cell layer of stratified epithelia, endocrine pancreas, and thymic medulla, with a pattern that did not overlap with that of another apoptosis inhibitor, bcl-2. A sequence-specific antibody to survivin immunoblotted a single approximately 16.5-kd survivin band in human fetal lung, liver, heart, kidney, and gastrointestinal tract. In mouse embryo, prominent and nearly ubiquitous distribution of survivin was found at embryonic day (E)11.5, whereas at E15 to -21, survivin expression was restricted to the distal bronchiolar epithelium of the lung and neural-crest-derived cells, including dorsal root ganglion neurons, hypophysis, and the choroid plexus. These data suggest that expression of survivin in embryonic and fetal development may contribute to tissue homeostasis and differentiation independently of bcl-2. Aberrations of this developmental pathway may result in prominent re-expression of survivin in neoplasia and abnormally prolonged cell viability.