共查询到20条相似文献,搜索用时 156 毫秒
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核心蛋白聚糖( Decorin,DCN)是富含亮氨酸小分子蛋白多糖家族成员之一,是公认的抑癌基因,可结合并灭活转化生长因子β( TGF-β)和抑制血管内皮生长因子( VEGF)表达,还可通过激活EG-FR/MAP激酶/p21信号通路介导的促细胞增殖信号通路等机制来抑制肿瘤细胞增殖与转移,在肿瘤的发展、血管形成、转移过程中具有重要作用. DCN在多种恶性肿瘤中表达,通过上调或下调DCN的表达,能够使DCN通过多种途径发挥其抗肿瘤活性,降低、延缓多种恶性肿瘤的发生、发展. DCN基因可能成为多种恶性肿瘤治疗的潜在靶点. 相似文献
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Hedgehog(HH)信号通路参与胚胎发育、成人组织再生及修复,且在肿瘤细胞生长及转移过程中发挥重要作用。已有大量研究证实该信号通路的异常激活与多种肿瘤的发生发展密切相关。Gli是HH通路直接调控靶基因的转录因子,是该通路不同水平激活的最后共同通道,在致瘤过程中起着重要作用。Gli受多通路多因素调节,故抑制Gli靶向性治疗具有非常广阔的前景。本文对Hedgehog-Gli信号通路在恶性肿瘤发生发展中的作用、Gli转录活性的调控及致瘤作用、Gli转录因子的靶向治疗价值等方面的研究进展进行综述。 相似文献
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刘莲叶 《国外医学(肿瘤学分册)》2005,32(10):739-742
抑癌基因CpG岛的异常甲基化可引起其转录抑制,基因失活,从而造成功能异常,导致恶性肿瘤发生.FHIT基因的甲基化与多种肿瘤的发生有关,因此对其甲基化的检测在恶性肿瘤的早期诊断、治疗及预后判断中具有重要意义. 相似文献
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抑癌基因CpG岛的异常甲基化可引起其转录抑制,基因失活,从而造成功能异常,导致恶性肿瘤发生.FHIT基因的甲基化与多种肿瘤的发生有关,因此对其甲基化的检测在恶性肿瘤的早期诊断、治疗及预后判断中具有重要意义. 相似文献
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Hedgehog(Hh)信号通路在胚胎发育、细胞增殖和分化中起着重要的调节作用,此通路异常激活可能会导致全身恶性肿瘤(肺癌、胃癌)的发生,尤其是口腔鳞癌的发生,因此Hh信号通路与口腔鳞癌密切相关。Hh信号通路主要有分泌型糖蛋白配体 Hedgehog(SHH)配体,跨膜蛋白受体Ptched(PTCH)受体,跨膜蛋白Smoothened(SMO),核转录因子GLI蛋白、Fu抑制子(SuFu)及下游目的基因组成。其中GLI1作为Hh信号通路的正向调控基因,起着激活Hh信号通路的作用。而SuFu作为Hh信号通路负向调控基因,起着抑制Hh信号通路的作用。本文就Hh信号通路在口腔鳞癌中信号传导机制及其相关基因GLI1、SuFu的研究进展进行综述,为未来口腔鳞癌的治疗、诊断和预防提供依据。 相似文献
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Jiawen Zhang Yongbin Yang Zhenbo Zhang Yinyan He Zhiqiang Liu Yinhua Yu Sufang Wu Bin Cai Youji Feng 《Cancer letters》2013
Gankyrin has been implicated in the formation of multiple cancer types, although its roles in estrogen-driven endometrial carcinoma remain unclarified. We evaluated the expression of Gankyrin in endometrial tissues and further explored its roles in estrogen-driven and GPR30-mediated endometrial cancer cell proliferation. Gankyrin was overexpressed in endometrial carcinoma tissues and showed an inverse relationship with the pattern of PTEN expression. The depletion or overexpression of Gankyrin induced endometrial cancer cell proliferation inhibition or expansion, respectively, which was associated with estrogen-driven GPR30 signaling via the PTEN/PI3K/AKT pathway. This study suggests that Gankyrin is functional in endometrial cancer development. 相似文献
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目的:探讨音猬因子(Shh)、Smoothened(Smo)基因在宫颈鳞状细胞癌中的表达及意义.方法:采用反转录-聚合酶链反应(RT-PCR)和Westem blot检测76例宫颈鳞状细胞癌组织和42例正常宫颈组织中Shh、Smo mRNA和蛋白的表达情况.结果:RT-PCR检测结果显示,Shh、Smo mRNA在宫颈鳞状细胞癌中相对表达量分别为0.715±0.048、0.638±0.037,在正常宫颈组织中分别为0.341±0.072、0.311±0.051(P<0.05).Western blot检测结果显示,Shh、Smo蛋白在宫颈鳞状细胞癌中的相对表达量分别为0.568±0.013、0.521±0.056,在正常宫颈组织中分别为0.281±0.047、0.252±0.064(P<0.05).宫颈鳞状细胞癌组织Shh、Smo mRNA和蛋白平均表达水平高于正常宫颈组织,差异有统计学意义(P<0.05);Shh、Smo mRNA和蛋白表达水平与宫颈鳞状细胞癌的分化程度明显相关(P<0.05),与患者年龄、FIGO分期、侵犯血管和神经、淋巴结转移、远处转移无明显相关(P>0.05).结论:宫颈鳞状细胞癌组织中Shh、Smo蛋白呈高表达,Shh、Smo蛋白的高表达可能与宫颈鳞状细胞癌的发生、发展及转移关系密切. 相似文献
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The hedgehog (Hh) signal pathway has recently been shown to be activated in human malignancies. However, little is known about its role in the development or patient prognosis of epithelial ovarian carcinoma. In the present study, we examined in vivo and in vitro the expression and functional role of Hh signal molecules in epithelial ovarian tumors and normal ovarian surface epithelial (OSE) cells. The expression of Shh, Dhh, Ptch, Smo and Gli1 proteins was not observed in normal OSE, but was increased stepwise in benign, borderline and malignant neoplasms. In addition, immunoreactivity for Shh, Dhh, Ptch, Smo and Gli1 was highly correlated with cell proliferation assessed by Ki-67. Blocking the Hh signal using either the Hh pathway inhibitor cyclopamine or Gli1 siRNA led to remarkably decreased cell proliferation in ovarian carcinoma cells. Treatment with cyclopamine induced not only G, arrest but also apoptosis along with the downregulation of cyclin A and cyclin D1, and the upregulation of p21 and p27. Among the Hh signal molecules, Dhh expression was correlated with poor prognosis of ovarian carcinoma patients. These findings suggest that the Hh signal pathway plays an important role in ovarian tumorigenesis as well as in the activation of cell proliferation in ovarian carcinomas. Thus, the Hh signal pathway is a possible molecular target of new treatment strategies for ovarian carcinoma. 相似文献
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Yong An Baobao Cai Jianmin Chen Nan Lv Jie Yao Xiaofeng Xue Min Tu Dong Tang Jishu Wei Kuirong Jiang Junli Wu Qiang Li Wentao Gao Yi Miao 《Cancer letters》2013
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal human malignancies and is regulated by Sonic Hedgehog (Shh) signaling. Recently, MAP3K10 has been shown to regulate Shh signaling, suggesting a role for MAP3K10 in the tumorigenesis of PDAC. We determined the expression status of MAP3K10 in PDAC tissues and cell lines, and analyzed the viability and cell proliferation of PDAC cells with an overexpression or knockdown of MAP3K10 in vitro. MAP3K10 was upregulated in PDAC tissues and cell lines. Overexpression of MAP3K10 promoted the proliferation and decreased the gemcitabine sensitivity of pancreatic cancer cells. In contrast, knockdown of MAP3K10 significantly decreased cell proliferation and sensitized cells to gemcitabine. However, neither overexpression nor knockdown of MAP3K10 affected cell migration. Moreover, overexpression of MAP3K10 resulted in upregulation of Gli-1 and Gli-2 in PDAC cells. Our results indicate a novel and important role for MAP3K10 in the proliferation and chemoresistance of PDAC. Our study suggests that targeting MAP3K10 is a potential strategy for the development of alternative therapies for pancreatic cancers. 相似文献
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Nakamura M Kubo M Nagai S Yamaguchi K Tanaka M Katano M 《Gan to kagaku ryoho. Cancer & chemotherapy》2007,34(12):1914-1916
The hedgehog (Hh) signaling pathway was originally found as an organizer in embryonic development. The pathway is now implicated in the development of various tumors. Recently, it has been reported that the pathway activation is resulted from aberrant expression of the ligand, Sonic Hh (Shh), in pancreatic cancer and breast cancer. Here we developed a new strategy to control the activation of the Hh signaling pathway in cancer cells, which have ectopic and ligand dependent activation of the Hh signaling pathway. Our strategy may contribute to the development of a new cancer treatment. 相似文献
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FOXM1 is a downstream target of Gli1 in basal cell carcinomas 总被引:10,自引:0,他引:10
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Yu-Zhen Feng Tanri Shiozawa Tsutomu Miyamoto Hiroyasu Kashima Miyuki Kurai Akihisa Suzuki Jiang Ying-Song Ikuo Konishi 《Clinical cancer research》2007,13(5):1389-1398
PURPOSE: Research has revealed abnormal activation of the hedgehog pathway in human malignancies. The present study was undertaken to examine the expression and functional involvement of the hedgehog pathway in endometrial tissues. EXPERIMENTAL DESIGN: The expression of sonic hedgehog (Shh), patched (Ptch), Smoothened (Smo), and Gli1 was examined in various endometrial tissues and endometrial carcinoma cell lines. The effect of hedgehog signaling on the proliferation of endometrial carcinoma cell lines was also examined. RESULTS: The expression of Shh, Ptch, Smo, and Gli1 was very weak in normal endometrium, but was increased in endometrial hyperplasia and carcinoma stepwisely with significant differences. There was no marked difference in the expression of these molecules in carcinomas according to stages and histologic grades. Treatment with cyclopamine, a specific inhibitor of the hedgehog pathway, for endometrial carcinoma Ishikawa and HHUA cells suppressed growth by 56% and 67%, respectively, compared with the control. The addition of recombinant Shh peptide to HHUA cells enhanced their proliferation by 41%. The silencing of Gli1 using small interfering RNA (siGli1) resulted in the growth suppression and down-regulation of Ptch expression. In addition, the cyclopamine/siGli1-induced growth suppression was associated with the down-regulation of cyclins D1 and A and N-myc. No somatic mutations for ptch and smo genes were detected in the endometrial carcinoma cases examined. CONCLUSIONS: The abnormal activation of this pathway is involved in the proliferation of endometrial carcinoma cells possibly in an auto-/paracrine fashion, suggesting the possibility of the hedgehog pathway being a novel candidate for molecular targeting. 相似文献
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Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1(+/-)p53(-/-) mice 总被引:9,自引:0,他引:9
Romer JT Kimura H Magdaleno S Sasai K Fuller C Baines H Connelly M Stewart CF Gould S Rubin LL Curran T 《Cancer cell》2004,6(3):229-240
Medulloblastoma is the most common malignant pediatric brain tumor. Current treatment is associated with major long-term side effects; therefore, new nontoxic therapies, targeting specific molecular defects in this cancer, need to be developed. We use a mouse model of medulloblastoma to show that inhibition of the Sonic Hedgehog (Shh) pathway provides a novel therapy for medulloblastoma. A small molecule inhibitor of the Shh pathway, HhAntag, blocked the function of Smoothened in mice with medulloblastoma. This resulted in suppression of several genes highly expressed in medulloblastoma, inhibition of cell proliferation, increase in cell death and, at the highest dose, complete eradication of tumors. Long-term treatment with HhAntag prolonged medulloblastoma-free survival. These findings support the development of Shh antagonists for the treatment of medulloblastoma. 相似文献
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The Hedgehog (Hh) pathway is a major regulator of many fundamental processes in vertebrate embryonic development including stem cell maintenance, cell differentiation, tissue polarity and cell proliferation. Constitutive activation of the Hh pathway leading to tumorigenesis is seen in basal cell carcinomas and medulloblastoma. A variety of other human cancers, including brain, gastrointestinal, lung, breast and prostate cancers, also demonstrate inappropriate activation of this pathway. Paracrine Hh signaling from the tumor to the surrounding stroma was recently shown to promote tumorigenesis. This pathway has also been shown to regulate proliferation of cancer stem cells and to increase tumor invasiveness. Targeted inhibition of Hh signaling may be effective in the treatment and prevention of many types of human cancers. The discovery and synthesis of specific Hh pathway inhibitors have significant clinical implications in novel cancer therapeutics. Several synthetic Hh antagonists are now available, several of which are undergoing clinical evaluation. The orally available compound, GDC-0449, is the farthest along in clinical development. Initial clinical trials in basal cell carcinoma and treatment of select patients with medulloblastoma have shown good efficacy and safety. We review the molecular basis of Hh signaling, the current understanding of pathway activation in different types of human cancers and we discuss the clinical development of Hh pathway inhibitors in human cancer therapy. 相似文献