Differentiation-associated genes regulated by c-Jun and decreased in the progression of esophageal squamous cell carcinoma.
Differentiation-associated genes regulated by c-Jun and decreased in the progression of esophageal squamous cell carcinoma.
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食管鳞状细胞癌进展中受 c-Jun 调控并减少的分化相关基因
DOI：
10.1371/journal.pone.0096610
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Luo A;Yu X;Li G;Ma G;Chen H;Ding F;Li Y;Liu Z
转录因子c-Jun在控制上皮细胞增殖、凋亡和分化中发挥关键作用。然而，c-Jun在食管鳞状细胞癌（ESCC）鳞状细胞分化和进展中的分子机制和生物学功能仍不清楚。在本研究中，我们发现c-Jun直接与启动子区域结合，并在体内激活分化相关基因（包括胱抑素A、外皮蛋白和SPRR3）的转录。 c-Jun 的异位表达增强了 KYSE450 细胞中 SPRR3 的反式激活。相反，c-Jun 的显性失活突变体 TAM67 抑制 SPRR3 反式激活。 c-Jun 主要通过 PKC/JNK 途径响应 KYSE450 细胞中的 TPA 增加 SPPR3 的表达。此外，c-Jun在食道癌中显着减少。有趣的是，胱抑素 A、外皮蛋白和 SPRR3 也显着下调，并且与分化等级相关。 c-Jun 的表达与正常上皮和 ESCC 中这些基因的表达相关。重要的是，在从正常上皮恶性转化为低级别上皮内瘤变（LGIN）或高级别上皮内瘤变（HGIN）的过程中，这些基因的表达显着降低。从LGIN到HGIN，胱抑素A和外皮蛋白的表达显着降低。这些结果表明 c-Jun 参与 ESCC 中分化相关基因的调节。这些基因可能作为区分正常上皮和食管鳞状上皮内瘤变的潜在标记。
Transcription factor c-Jun plays a key role in controlling epithelium cell proliferation, apoptosis and differentiation. However, molecular mechanism and biological functions of c-Jun in squamous differentiation and the progression of esophageal squamous cell carcinoma (ESCC) remain elusive. In this study, we found that c-Jun bound directly to the promoter region, and activated the transcription of differentiation-associated genes including cystatin A, involucrin and SPRR3 in vivo. Ectopic expression of c-Jun enhanced SPRR3 transactivation in KYSE450 cells. Conversely, TAM67, a dominant negative mutant of c-Jun, inhibited SPRR3 transactivation. c-Jun increased expression of SPPR3 mainly via a PKC/JNK pathway in response to TPA in KYSE450 cells. Furthermore, c-Jun was remarkably reduced in esophageal cancer. Interestingly, cystatin A, involucrin and SPRR3 were significantly downregulated as well, and associated with differentiation grade. Expression of c-Jun was correlated with the expression of these genes in normal epithelium and ESCC. Importantly, the expression of these genes was remarkably decreased during the malignant transformation from normal epithelium to low-grade intraepithelial neoplasia (LGIN) or high-grade intraepithelial neoplasia (HGIN). The expression of cystatin A and involucrin was significantly reduced from LGIN to HGIN. These results suggest c-Jun was involved in the regulation of differentiation-associated genes in ESCC. These genes might serve as the potential markers in distinguishing normal epithelium from esophageal squamous intraepithelial neoplasia.
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影响因子：
6.5
作者：
MURPHY, GF;FLYNN, TC;PINKUS, GS
通讯作者：
PINKUS, GS
影响因子：
--
作者：
Lehrbach, Dárcio Matenhauer;Nita, Marcelo Eidi;Cecconello, Ivan
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Cecconello, Ivan
DOI：
10.1016/s1383-5742(00)00019-3
发表时间：
2000-04-01
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
6.5
作者：
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通讯作者：
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影响因子：
7.8
作者：
Eferl, R;Sibilia, M;Hilberg, F;Fuchsbichler, A;Kufferath, I;Guertl, B;Zenz, R;Wagner, E F;Zatloukal, K
通讯作者：
Zatloukal, K