Uchide Tsuyoshi, Takatsu Norihiro, Fujimori Yuki, Fukushima Ushio, Itoh Hiroshi
Laboratory of Toxicology, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
DNA Seq. 2005 Oct;16(5):329-34. doi: 10.1080/10425170500213696.
Survivin, a member of the inhibitor of apoptosis (IAP) gene family, overexpresses in various human tumors. Recently this protein has attracted strong interest as a potential prognostic marker because it promotes malignancy through anti-apoptotic activity and is associated with a more aggressive phenotype. To explore the utility of survivin as a veterinary marker of tumor malignancy, we performed molecular cloning of dog survivin cDNA and studied survivin mRNA expression in a variety of naturally occurring dog tumors. The dog cDNA contains a 426-bp open reading frame encoding 142 amino acids of polypeptide, in which a structure termed the baculovirus IAP repeat (BIR) domain, commonly observed in IAPs, is found, as it is in other mammalian survivin protein. The transcript was detected in many adult normal organs including heart, lung, liver, stomach, duodenum, colon, spleen, kidney and testis. As a result of quantitative expression analysis by real-time PCR undertaken for benign and malignant tumors, overexpression of the survivin gene was found in 3 of 18 malignant tumors and in none of the benign tumors, suggesting that survivin overexpression is associated with tumor malignancy in dog.
生存素是凋亡抑制蛋白（IAP）基因家族的成员之一，在多种人类肿瘤中过度表达。最近，这种蛋白作为一种潜在的预后标志物引起了强烈关注，因为它通过抗凋亡活性促进恶性肿瘤发展，并且与更具侵袭性的表型相关。为了探索生存素作为肿瘤恶性程度的兽医标志物的实用性，我们对犬生存素cDNA进行了分子克隆，并研究了其在多种自然发生的犬类肿瘤中的mRNA表达。犬cDNA包含一个426 bp的开放阅读框，编码142个氨基酸的多肽，其中发现了一个在IAP中常见的称为杆状病毒IAP重复（BIR）结构域的结构，其他哺乳动物的生存素蛋白中也存在该结构。在包括心脏、肺、肝脏、胃、十二指肠、结肠、脾脏、肾脏和睾丸在内的许多成年正常器官中均检测到了该转录本。通过对良性和恶性肿瘤进行实时PCR定量表达分析，发现18个恶性肿瘤中有3个存在生存素基因的过度表达，而良性肿瘤中均未发现，这表明生存素的过度表达与犬类肿瘤的恶性程度相关。
