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標題: 犬惡性乳腺腫瘤之HER2蛋白表現及核苷酸序列分析
HER2 Protein Expression and Nucleotide Sequence Analysis in Canine Malignant Mammary Tumors
作者: 黃惠敏
Huang, Hui-Min
關鍵字: dogs

malignant mammary tumors
HER2 nucleotide sequence
出版社: 獸醫學系暨研究所
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摘要: 人類上皮生長因子接受器2 (HER2) 為一個跨膜醣蛋白,已被證實與人類的乳癌有關係。20-30% 之乳癌患者有HER2過度表現的現象,且HER2基因已被發現有exon 16缺失和codon 655多型性,而codon 655之胺基酸可為valine 或isoleucine。此外乳癌患者的HER2過度表現也代表不好的預後。犬HER2基因位於染色體1q13.1。前人的研究已經發現犬的乳腺腫瘤有HER2基因增幅和HER2蛋白過度表現,但是目前還未有研究同時分析犬惡性乳腺腫瘤HER2蛋白的過度表現和手術後存活的關係,也沒有完整HER2核酸序列分析之研究。本實驗目的為偵測犬惡性乳腺腫瘤之HER2蛋白表現和分析犬HER2之核苷酸序列。 本實驗收集91個犬惡性乳腺腫瘤組織,使用免疫組織化學法偵測HER2蛋白表現。如同人類的結果犬惡性乳腺腫瘤之HER2蛋白表現為29.7% (27/91)。經過2年術後的存活分析發現HER2陽性的患犬存活時間較HER2陰性的患犬長。接著我們挑選部分樣本進行HER2 exon14-18和全長cDNA的序列分析。所有的序列皆分別地與正常犬之HER2 genomic DNA (GenBank NC006591) 和complementary DNA (GenBank AB008451) 比對。結果發現犬惡性乳腺腫瘤的HER2基因序列不像人一樣有exon 16缺失和codon 655多型性的現象,只有核苷酸1725有單一核苷酸多型性的現象但是胺基酸並沒有改變皆為cysteine。因此,我們推測HER2蛋白的過度表現在犬惡性乳腺腫瘤的發育起始點扮演一個重要的角色,但是還不足以可以當成一個獨立的預後因子。
Human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein receptor, has been shown to be involved in carcinogenesis of human breast cancer and is associated with poor prognosis. It has been shown that HER2 overexpression contributes to 20-30% of human breast carcinoma. HER2 lacking exon 16 is represented in some cases of human breast carcinoma, while a polymorphism at codon 655 (GTC/valine or ATC /isoleucine) has been identified in other cases. The canine HER2 gene has been mapped to chromosome 1q13.1. Previous studies have shown that either HER2 gene amplification or HER2 protein overexpression are present in canine mammary tumors, but none has addressed the simultaneous analysis of HER2 protein expression and the relationship between post-surgery survival time in canine malignant mammary tumors. Besides, there are no studies exploring the contribution of the HER2 gene to canine mammary tumors. The aims of this study are to exam HER2 protein expression and analyze the HER2 nucleotide acid sequence in canine malignant mammary tumors. In this study, tissue specimens collected from a series of 91 dogs with malignant mammary tumors were analyzed for expression of HER2 by immunohistochemistry. HER2 protein overexpression was detected in 29.7% (27/91) of the canine malignant mammary tumors. After 2 years survival analysis, we found that HER2 positive dogs with malignant mammary tumors tended to have longer survival time than those that did not overexpress HER2. Subsequently, samples were chosen for sequence analysis of the cDNA region from exon14 to 18 and whole cDNA in HER2 gene. All samples were compared with normal HER2 gDNA (GenBank NC006591) and with cDNA (GenBank AB008451), respectively. Neither exon 16 deletion nor codon 655 polymorphism was found in the HER2 gene of canine malignant mammary tumors. However, 3 out of 19 (15.8 %) cases had single nucleotide polymorphism (SNP) in HER2 gene, T1725C, but the amino acid was not changed (Cys-Cys). Hence, our results suggested that overexpression of HER2 may play a role in the development of canine malignant mammary tumors, but it is not adequate for serving as an independent prognostic factor.
其他識別: U0005-2407200720313500
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