المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Supplementary Figure 3 from Transforming Growth Factor β1 Promotes Chromosomal Instability in Human Papillomavirus 16 E6E7–Infected Cervical Epithelial Cells

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::024ebeab7a820bb61eeedb76effc0665
https://doi.org/10.1158/0008-5472.22371150

المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Supplementary Figure 4 from Transforming Growth Factor β1 Promotes Chromosomal Instability in Human Papillomavirus 16 E6E7–Infected Cervical Epithelial Cells

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62356c78601e84e2a78433c39a1b2565
https://doi.org/10.1158/0008-5472.22371147.v1

المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Uterine cervical cancer, the second most frequently occurring cancer in women worldwide, is tightly associated with the expression of high-risk human papillomavirus [mainly human papillomavirus (HPV)-16 and HPV18] oncogenes E6 and E7 and characteristically exhibits chromosomal instability. However, the mechanisms underlying chromosomal instability in cervical cancer are still not fully understood. In this study, we observed that two of three human cervical epithelial cell lines expressing HPV16 E6E7 became immortalized without extensive chromosomal instability and crisis. The introduction of transforming growth factor (TGF)-β1, a multiple functional cytokine/growth factor, in the culture medium induced crisis, which was associated with massive chromosomal end-to-end fusions and other structural aberrations. The distributions of structural aberrations on individual chromosomes were significantly correlated with the profiles of telomere signal–free ends. The immortalized cells that emerged from the TGF-β1–induced crisis showed multiple clonal structural aberrations that were not observed in cells without TGF-β1 treatment. Overexpression of the catalytic subunit of telomerase (hTERT) abolished the effects of TGF-β1 on chromosomal instability. Interestingly, another HPV16 E6E7–expressing cervical cell line that experienced crisis and telomere dysfunction under ordinary culture condition had a higher level of autocrine TGF-β1 production than the other two crisis-free immortalized cell lines. Blocking the TGF-β1 pathway by an inhibitor of TGF-β1 receptor type I prevented the crisis and telomere-mediated chromosomal instability. In addition, more dramatic telomere shortening was observed in cervical intraepithelial neoplasias having higher expression of TGF-β1 in vivo. These results together suggest an important role of TGF-β1 in the early process of cervical carcinogenesis. [Cancer Res 2008;68(17):7200–9]

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::05abb45aafa4268b6bbb9039391e63ca
https://doi.org/10.1158/0008-5472.c.6496683

المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Supplementary Figure 1 from Transforming Growth Factor β1 Promotes Chromosomal Instability in Human Papillomavirus 16 E6E7–Infected Cervical Epithelial Cells

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0473c313d56b8cd2d93a35c112f650d3
https://doi.org/10.1158/0008-5472.22371156

المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Supplementary Table 1 from Transforming Growth Factor β1 Promotes Chromosomal Instability in Human Papillomavirus 16 E6E7–Infected Cervical Epithelial Cells

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::314534dff673c6a1e8cdee62a5919e35
https://doi.org/10.1158/0008-5472.22371144.v1

المؤلفون: Annie L.M. Cheung, Xin-Yuan Guan, Hui Yao Lan, Annie N.Y. Cheung, Hextan Y.S. Ngan, Chi M. Tsang, Si Liu, Xiao Ru Huang, Esther Wong, Yvonne K. Kwok, Sai Wah Tsao, Wen Deng

الوصف: Supplementary Figure 2 from Transforming Growth Factor β1 Promotes Chromosomal Instability in Human Papillomavirus 16 E6E7–Infected Cervical Epithelial Cells

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3405578a6a89eedf00328be18a82a360
https://doi.org/10.1158/0008-5472.22371153.v1

المؤلفون: Nai-dy Wang, Shing Chuan Hooi, Esther Wong, Sathivel Ponniah, Ee Hong Tan, Mirtha Laban, Aileen Wee

المصدر: Cancer Research. 65:10330-10337

مصطلحات موضوعية: Cyclin-Dependent Kinase Inhibitor p21, Cancer Research, Mice, Transgenic, Cell Growth Processes, Biology, Mice, chemistry.chemical_compound, Liver Neoplasms, Experimental, CCAAT-Enhancer-Binding Protein-alpha, medicine, Animals, Genetic Predisposition to Disease, RNA, Messenger, Promoter Regions, Genetic, Protein kinase A, Protein kinase B, Alleles, Cell Nucleus, Reporter gene, Binding protein, Liver Glycogen, Vascular endothelial growth factor, Glycogen Synthase, Liver, Oncology, chemistry, Mechanism of action, Cancer research, Phosphorylation, alpha-Fetoproteins, Signal transduction, medicine.symptom

الوصف: Hypoxia-inducible factor 1 (HIF-1) is the central mediator of cellular responses to low oxygen and has recently become an important therapeutic target for solid tumor therapy. Inhibition of HIF-1 is expected to result in the attenuation of hypoxia-inducible genes, which are vital to many aspects of tumor biology, including adaptative responses for survival under anaerobic conditions. To identify small molecules inhibiting the HIF-1 pathway, we did a biological screen on a 10,000-membered natural product-like combinatorial library. The compounds of the library, which share a 2,2-dimethylbenzopyran structural motif, were tested for their ability to inhibit the hypoxic activation of an alkaline phosphatase reporter gene under the control of hypoxiaresponsive elements in human glioma cells. This effort led to the discovery of 103D5R, a novel small-molecule inhibitor of HIF-1a. 103D5R markedly decreased HIF-1a protein levels induced by hypoxia or cobaltous ions in a dose- and timedependent manner, whereas minimally affecting global cellular protein expression levels, including that of control proteins such as HIF-1h ,I nBaa, and hh-actin. The inhibitory activity of 103D5R against HIF-1a was clearly shown under normoxia and hypoxia in cells derived from different cancer types, including glioma, prostate, and breast cancers. This inhibition prevented the activation of HIF-1 target genes under hypoxia such as vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). Investigations into the molecular mechanism showed that 103D5R strongly reduced HIF-1a protein synthesis, whereas HIF-1a mRNA levels and HIF-1a degradation were not affected. 103D5R inhibited the phosphorylation of Akt, Erk1/2, and stressactivated protein kinase/c-jun-NH2-kinase, without changing the total levels of these proteins. Further studies on the mechanism of action of 103D5R will likely provide new insights into its validity/applicability for the pharmacologic targeting of HIF-1aa for therapeutic purposes. (Cancer Res 2005; 65(2): 605-12)

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82d3f2325b8a28f1ac6d1ea99077fa0d
https://doi.org/10.1158/0008-5472.can-04-4486