Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenesis
Altered gene expression of transcriptional regulatory factors in tumor marker-positive cells during chemically induced hepatocarcinogenesis
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DOI：
10.1016/j.toxlet.2006.08.014
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发表时间：
2006-12-01
影响因子：
3.5
通讯作者：
Nishihara, Tsutomu
中科院分区：
文献类型：
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作者：
Osada, Shigehiro;Naganawa, Ayako;Nishihara, Tsutomu
胎盘型谷胱甘肽-S-转移酶 (GST-P) 在大鼠化学性肝癌发生中具有显着且特异的诱导性，是肿瘤前期的可靠标记蛋白。为了深入了解肝癌发生和肝毒性早期的分子机制，我们通过 DNA 微阵列分析研究了基因表达谱。我们从三只大鼠的 GST P 阳性灶中制备了 RNA，并与三只大鼠的正常肝切片进行比较，并将标记的 RNA 单独杂交到 Affymetrix GeneChip 大鼠表达阵列 230A 上。 DNA微阵列分析显示了明显不同的失调基因表达谱，并支持了之前的发现，即一些参与代谢和解毒的酶被过度表达和抑制。在这里，我们发现一些 DNA 结合转录因子和辅助因子，包括甾醇调节元件结合蛋白 1 (SREBP1) 和维尔姆斯肿瘤 1 (WT1) 相互作用蛋白，及其靶基因在 GST-P 阳性病灶中失调。此外，涉及染色质成分、组蛋白修饰酶和中心体复制的基因也高度表达。此前并不知道这些基因在化学诱导的肝癌发生过程中会上调。使用从肿瘤标志物阳性病灶和对照组织制备的 RNA 进行 DNA 微阵列分析，提供了与癌发生和肝毒性早期阶段相关的候选基因。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Glutathione-S-transferase placental form (GST-P) is markedly and specifically inducible in rat chemical hepatocarcinogenesis and is a reliable marker protein for pre-neoplasia. To gain insights into the molecular mechanisms at the early stage of hepatocarcinogenesis and hepatotoxicity, we investigated the gene expression profile by DNA microarray analysis. We prepared RNA from GST P-positive foci in three individual rats and compared with normal liver sections from three individual rats, and labeled RNA was individually hybridized onto Affymetrix GeneChip Rat Expression Array 230A. DNA microarray analysis showed distinctly different profiles of dysregulated gene expression and supported the previous finding that some enzymes involved in metabolism and detoxification are overexpressed and suppressed. Here we discovered that several DNA-binding transcription factors and cofactors, including sterol-regulatory-element binding protein 1 (SREBP1) and Wilms' tumour 1 (WT1)-interacting protein, and their target genes were dysregulated in GST-P-positive foci. Moreover, genes involved in chromatin components, histone modification enzymes, and centrosome duplication were highly expressed. These genes were not previously known to be up-regulated during chemically induced hepatocarcinogenesis. DNA microarray analysis using RNA prepared from tumor marker-positive foci and control tissues provided a candidate gene link to the early stage of carcinogenesis and hepatotoxicity. (c) 2006 Elsevier Ireland Ltd. All rights reserved.