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犬皮肤黑色素瘤中 Wnt/β-连环蛋白信号通路的失调。

Dysregulation of the Wnt/beta-catenin signaling pathway in canine cutaneous melanotic tumor.

机构信息

Veterinary Laboratory Medicine, College of Veterinary Medicine, Chungbuk National University, Chungbuk, South Korea.

出版信息

Vet Pathol. 2010 Mar;47(2):285-91. doi: 10.1177/0300985809359303. Epub 2009 Dec 31.

DOI:10.1177/0300985809359303
PMID:20139375
Abstract

The Wnt/beta-catenin signal transduction pathway is important in many developmental processes and during tumorigenesis. beta-Catenin acts as a signal transducer. To investigate whether the Wnt/beta-catenin signal transduction pathway is involved in canine cutaneous melanomagenesis, 18 formalin-fixed paraffin-embedded canine cutaneous melanotic tumor tissues were examined. For cloning and sequencing of the full-length canine ctnnb1 gene encoding beta-catenin, conserved sequences of the human and mouse ctnnb1 gene were used to design the primers. For analysis of expression and translocation of beta-catenin in canine cutaneous melanotic tumors, semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed. The canine ctnnb1 sequence showed a high degree of similarity to those of human and mouse. Semiquantitative RT-PCR showed a substantial increase in expression of ctnnb1 mRNA in canine cutaneous melanotic tumors compared to normal canine melanocytes, regardless of whether the tumor was benign or malignant. Immunohistochemistry revealed cytoplasmic accumulation of beta-catenin in melanotic tumors. In melanoma tissues, nuclear translocation of beta-catenin was also observed. The present study demonstrated that abnormal intracellular accumulation and substantially increased expression of beta-catenin are involved in canine cutaneous melanotic tumor.

摘要

Wnt/β-连环蛋白信号转导通路在许多发育过程和肿瘤发生中都很重要。β-连环蛋白作为信号转导物起作用。为了研究 Wnt/β-连环蛋白信号转导通路是否参与犬皮肤黑色素瘤的发生,检查了 18 例福尔马林固定石蜡包埋的犬皮肤黑色素瘤组织。为了克隆和测序编码β-连环蛋白的全长犬 ctnnb1 基因,使用了人 ctnnb1 基因和鼠 ctnnb1 基因的保守序列来设计引物。为了分析犬皮肤黑色素瘤中β-连环蛋白的表达和易位,进行了半定量逆转录聚合酶链反应(RT-PCR)和免疫组织化学分析。犬 ctnnb1 序列与人鼠 ctnnb1 序列高度相似。半定量 RT-PCR 显示,与正常犬黑素细胞相比,犬皮肤黑色素瘤中 ctnnb1 mRNA 的表达显著增加,无论肿瘤是良性还是恶性。免疫组织化学显示黑色素瘤组织中β-连环蛋白的细胞质积累。在黑色素瘤组织中,还观察到β-连环蛋白的核易位。本研究表明,β-连环蛋白的异常细胞内积累和表达增加与犬皮肤黑色素瘤有关。

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