共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
4.
Expression of human GLI in mice results in failure to thrive, early death, and patchy Hirschsprung-like gastrointestinal dilatation. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Molecular medicine (Cambridge, Mass.)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J. T. Yang C. Z. Liu E. H. Villavicencio J. W. Yoon D. Walterhouse P. M. Iannaccone 《Molecular medicine (Cambridge, Mass.)》1997,3(12):826-835
5.
6.
7.
Novel human glioma-associated oncogene 1 (GLI1) splice variants reveal distinct mechanisms in the terminal transduction of the hedgehog signal 总被引:1,自引:0,他引:1
Shimokawa T Tostar U Lauth M Palaniswamy R Kasper M Toftgård R Zaphiropoulos PG 《The Journal of biological chemistry》2008,283(21):14345-14354
8.
Arai MA Tateno C Hosoya T Koyano T Kowithayakorn T Ishibashi M 《Bioorganic & medicinal chemistry》2008,16(21):9420-9424
The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. By screening tropical plant extracts by using our screening system, Zizyphus cambodiana was found to include Hh/GLI signaling inhibitors. Bioassay-guided fractionation of this plant extract led to the isolation of three active pentacyclic triterpenes, colubrinic acid (1), betulinic acid (2) and alphitolic acid (3), as potent inhibitors. The inhibition of GLI-related protein expression with 1 or 2 was observed in HaCaT cells with exogenous GLI1, or human pancreatic cancer cells (PANC1), which express Hh/GLI components aberrantly. The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited by 1 or 2. We also examined the cytotoxicity of these active compounds against PANC1, human prostate cancer cells (DU145) and mouse embryo fibroblast cells (C3H10T1/2). The cytotoxicity against cancer cells (PANC1 and DU145) by 1 or 2 would be caused by inhibition of the expression of the anti-apoptosis protein BCL2. These pentacyclic triterpene inhibitors showed an important relationship between Hh/GLI signaling inhibition, the decrease of BCL2, and cytotoxicity against cancer cells. 相似文献
9.
Dai P Akimaru H Tanaka Y Maekawa T Nakafuku M Ishii S 《The Journal of biological chemistry》1999,274(12):8143-8152
10.
11.
12.
Hedgehog signaling in normal urothelial cells and in urothelial carcinoma cell lines 总被引:1,自引:0,他引:1
Thievessen I Wolter M Prior A Seifert HH Schulz WA 《Journal of cellular physiology》2005,203(2):372-377
Constitutive activation of hedgehog signaling, often caused by PTCH1 inactivation and leading to inappropriate activation of GLI target genes, is crucial for the development of several human tumors including basal cell carcinoma of the skin and medulloblastoma. The PTCH1 gene at 9q22 is also considered as a candidate tumor suppressor in transitional cell carcinoma (TCC), of which >50% show LOH in this region. However, only rare mutations have been found in PTCH1. We have therefore investigated GLI-dependent promoter activity and expression of hedgehog pathway components in TCC cell lines and proliferating normal urothelial cells. Normal urothelial cells cultured in serum-free medium, but not TCC lines exhibited low, but significant promoter activity under standard growth conditions. Accordingly, GLI1-3 and PTCH1 mRNAs were expressed at moderate levels, and sonic hedgehog (SHH) mRNA expression was low to undetectable. In co-transfection experiments GLI1 increased promoter activity significantly in one TCC line and further in normal urothelial cells, but less strongly in other TCC lines. Expression patterns of GLI factor mRNAs did not correlate with inducibility. No significant effects of SHH or cyclopamine on proliferation were observed, ruling out autocrine effects. However, SHH induced GLI-dependent promoter activity in normal urothelial cells. Taken together, our data suggest that the hedgehog pathway is weakly active in normal adult urothelial cells and of limited importance in TCC. 相似文献
13.
14.
15.
16.
Ikuo Nakamura Maite G. Fernandez-Barrena Maria C. Ortiz-Ruiz Luciana L. Almada Chunling Hu Sherine F. Elsawa Lisa D. Mills Paola A. Romecin Kadra H. Gulaid Catherine D. Moser Jing-Jing Han Anne Vrabel Eric A. Hanse Nicholas A. Akogyeram Jeffrey H. Albrecht Satdarshan P. S. Monga Schuyler O. Sanderson Jesus Prieto Lewis R. Roberts Martin E. Fernandez-Zapico 《The Journal of biological chemistry》2013,288(29):21389-21398
17.
Fiaschi M Rozell B Bergström A Toftgård R Kleman MI 《The Journal of biological chemistry》2007,282(49):36090-36101
The Hedgehog signaling pathway regulates the development and function of numerous tissues and when mis-regulated causes tumorigenesis. To assess the role of a deregulated Hedgehog signaling pathway in the mammary gland we targeted the expression of the Hedgehog effector protein, GLI1, to mammary epithelial cells using a bigenic inducible system. A constitutively active Hedgehog signaling pathway resulted with 100% penetrance in an undifferentiated mammary lobuloalveolar network during pregnancy. GLI1-expressing transgenic females were unable to lactate and milk protein gene expression was essentially absent. The inability to lactate was permanent and independent of continued GLI1 transgene expression. An increased expression of the GLI1 response gene Snail coupled to reduced expression of E-cadherin and STAT5 in the transgenic mammary gland provides a likely molecular explanation, underlying the observed phenotypic changes. In addition, remodeling of the mammary gland after parturition was impaired and expression of GLI1 was associated with accumulation of cellular debris in the mammary ducts during involution, indicating a defect in the clearance of dead cells. Areas with highly proliferative epithelial cells were observed in mammary glands with induced expression of GLI1. Within such areas an increased frequency of cells expressing nuclear Cyclin D1 was observed. Taken together the data support the notion that correct regulation of Hedgehog signaling within the epithelial cell compartment is critical for pregnancy-induced mammary gland development and remodeling. 相似文献
18.
19.
Mingfeng Zhang Hong Wang Hongqi Teng Jueping Shi Yanding Zhang 《Histochemistry and cell biology》2010,134(4):327-335
The Sonic hedgehog (Shh) cascade is crucial for the patterning of the early lung morphogenesis in mice, but its role in the
developing human lung remains to be determined. In the present study, the expression patterns of SHH signaling pathway components,
including SHH, PTCH1, SMO, GLI1, GLI2 and GLI3 were examined by in situ hybridization and immunohistochemistry, and compared with the equivalent patterns in mice. Our results
showed that, as in mice, SHH was expressed in the epithelium of the developing human lung. However, SHH receptors (PTCH1 and SMO) and SHH signaling effectors (GLI1-3) were strongly detected in the human lung epithelium, but weakly in the mesenchyme, slightly different from their expressions
in mice. Furthermore, the expression levels of SHH signaling pathway genes in human lung, but not that of GLI1, were subsequently downregulated at the canalicular stage evaluated by real-time PCR, coincident with a decline in the developing
murine lung. In conclusion, in spite of slight differences, the considerable similarities of gene expression in human and
mice suggest that conserved molecular networks regulate mammalian lung development. 相似文献