Use of a rainbow trout oligonucleotide microarray to determine transcriptional patterns in aflatoxin B1-induced hepatocellular carcinoma compared to adjacent liver.

Use of a rainbow trout oligonucleotide microarray to determine transcriptional patterns in aflatoxin B1-induced hepatocellular carcinoma compared to adjacent liver.
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使用虹鳟鱼寡核苷酸微阵列确定黄曲霉毒素 B1 诱导的肝细胞癌与邻近肝脏的转录模式。

DOI:
10.1093/toxsci/kfi309
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发表时间:
2005
期刊:
Toxicological sciences : an official journal of the Society of Toxicology
影响因子:
--
通讯作者:
Williams,DavidE
Williams,DavidE
中科院分区:
--
文献类型:
--
作者:
Tilton,SusanC;Gerwick,LenaG;Hendricks,JerryD;Rosato,CapriceS;Corley-Smith,Graham;Givan,ScottA;Bailey,GeorgeS;Bayne,ChristopherJ;Williams,DavidE

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肝细胞癌(HCC)是世界范围内最常见的恶性肿瘤之一,其发生与许多环境因素有关,包括饮食污染物黄曲霉毒素B1(AFB 1)的摄入。过去40年的研究表明,虹鳟鱼(Oncorhynchus mykiss)是研究黄曲霉毒素B1诱导的肝癌发生的一个很好的研究模型;然而,对鳟鱼肿瘤分子水平的变化知之甚少。我们已经开发了一个虹鳟鱼寡核苷酸阵列包含1672个元素,代表超过1400个已知或可能与毒理学,比较免疫学,致癌,内分泌学和应激生理学相关的基因。在这项研究中,我们应用微阵列技术来检测虹鳟鱼肿瘤模型中AFB 1诱导的肝癌的基因表达。在鳟鱼胚胎中加入50 ppb的黄曲霉毒素B1,13个月后,从幼鱼中分离出对照肝脏、肿瘤和肿瘤邻近的肝脏组织。与非癌性邻近组织和假手术启动的对照肝脏相比,在组织学证实的HCC中确定全局基因表达。与非癌组织相比,我们观察到HCC中不同的基因调控模式,包括对细胞周期控制、转录、细胞骨架形成和急性期反应重要的基因的上调和参与药物代谢、脂质代谢和视黄醇代谢的基因的下调。有趣的是,在鳟鱼HCC中观察到的表达谱与在人类和啮齿动物HCC中发现的转录特征相似,进一步支持了该模型的有效性。总的来说,这些发现有助于更好地了解黄曲霉毒素B1诱导鳟鱼肝癌发生的机制,并确定在进化上分离超过4亿年的物种中对致癌作用重要的保守基因。
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its occurrence is associated with a number of environmental factors including ingestion of the dietary contaminant aflatoxin B1(AFB1). Research over the last 40 years has revealed rainbow trout (Oncorhynchus mykiss) to be an excellent research model for study of AFB1-induced hepatocarcinogenesis; however, little is known about changes at the molecular level in trout tumors. We have developed a rainbow trout oligonucleotide array containing 1672 elements representing over 1400 genes of known or probable relevance to toxicology, comparative immunology, carcinogenesis, endocrinology, and stress physiology. In this study, we applied microarray technology to examine gene expression of AFB1-induced HCC in the rainbow trout tumor model. Carcinogenesis was initiated in trout embryos with 50 ppb AFB1, and after 13 months control livers, tumors, and tumor-adjacent liver tissues were isolated from juvenile fish. Global gene expression was determined in histologically confirmed HCCs compared to noncancerous adjacent tissue and sham-initiated control liver. We observed distinct gene regulation patterns in HCC compared to noncancerous tissue including upregulation of genes important for cell cycle control, transcription, cytoskeletal formation, and the acute phase response and downregulation of genes involved in drug metabolism, lipid metabolism, and retinol metabolism. Interestingly, the expression profiles observed in trout HCC are similar to the transcriptional signatures found in human and rodent HCC, further supporting the validity of the model. Overall, these findings contribute to a better understanding of the mechanism of AFB1-induced hepatocarcinogenesis in trout and identify conserved genes important for carcinogenesis in species separated evolutionarily by more than 400 million years.
DOI: 10.1182/blood-2002-04-1260
发表时间: 2002-11-15
期刊: BLOOD
影响因子: 20.3
作者:
Weinstein, DA;Roy, CN;Andrews, NC
通讯作者: Andrews, NC
DOI: 10.1093/bioinformatics/17.11.1067
发表时间: 2001-11-01
期刊: BIOINFORMATICS
影响因子: 5.8
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通讯作者: Stormo, GD
DOI: 10.1093/carcin/22.8.1271
发表时间: 2001-08-01
期刊: CARCINOGENESIS
影响因子: 4.7
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Ficazzola, MA;Fraiman, M;Walden, PD
通讯作者: Walden, PD
DOI: --
发表时间: 1968
期刊: Journal of the National Cancer Institute
影响因子: --
作者:
R. Sinnhuber;J. Wales;J. L. Ayres;R. H. Engebrecht;D. Amend
通讯作者: D. Amend
DOI: 10.1139/cjpp-74-2-203
发表时间: 1996-02-01
影响因子: 2.1
作者:
Groopman, JD;Wang, JS;Scholl, P
通讯作者: Scholl, P