Abstract 3268: Gene expression associated to relapsing disease in Wilms tumor indicates a more differentiated phenotype unveiling a distinct transformation process for patients with a higher risk of relapse

Kaffir lime (Citrus hystrix) is a plant member of family Rutaceae, and its leaves are commonly used in folk medicine. The present study explores antileukemic effects of the extracts and purified active compounds from the leaves. The antileukemic activity was investigated via inhibition of Wilms’ tumor 1 (WT1), which is a protein that involves in leukemic cell proliferation. In addition, the compounds were investigated for their effects on WT1 gene expression using real time RT-PCR and Western blotting. Cell cycle arrest and total cell number were investigated using flow cytometry and trypan blue exclusion method, respectively. The results demonstrated that the hexane fractionated extract had the greatest inhibitory effect on WT1 gene expression of many leukemic cell lines and significantly decreased WT1 protein levels of K562 cells (representative of the leukemic cells), in a dose- and time-dependent manner. Subfraction No. 9 (F9) after partial purification of hexane fractioned extract showed the highest suppression on WT1 protein and suppressed cell cycle at G2/M. The organic compounds were isolated from F9 and identified as phytol and lupeol. The bioassays confirmed antiproliferative activities of natural products phytol and lupeol. The results demonstrated anticancer activity of the isolated phytol and lupeol to decrease leukemic cell proliferation.

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Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter

Physiological Genomics ◽

10.1152/physiolgenomics.00046.2001 ◽

2001 ◽

Vol 7 (2) ◽

pp. 187-200 ◽

Cited By ~ 33

Author(s):

TAE HO LEE ◽

JERRY PELLETIER

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Transcription Factor ◽

Vitamin D Receptor ◽

Binding Sites ◽

Wilms Tumor ◽

Cdna Array ◽

Transcriptional Level ◽

Vdr Gene ◽

Downstream Target

The Wilms’ tumor suppressor gene, wt1, encodes a zinc finger transcription factor that can regulate gene expression. It plays an essential role in tumorigenesis, kidney differentiation, and urogenital development. To identify WT1 downstream targets, gene expression profiling was conducted using a cDNA array hybridization approach. We confirm herein that the human vitamin D receptor (VDR), a ligand-activated transcription factor, is a WT1 downstream target. Nuclear run on experiments demonstrated that the effect of WT1 on VDR expression is at the transcriptional level. Transient transfection assays, deletion mutagenesis, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays suggest that, although WT1 is presented with a possibility of three binding sites within the VDR promoter, activation of the human VDR gene appears to occur through a single site. This site differs from a previously identified WT1-responsive site in the murine VDR promoter (Maurer U, Jehan F, Englert C, Hübinger G, Weidmann E, DeLucas HF, and Bergmann L. J Biol Chem 276: 3727–3732, 2001). We also show that the products of a Denys-Drash syndrome allele of wt1 inhibit WT1-mediated transactivation of the human VDR promoter. Our results indicate that the human VDR gene is a downstream target of WT1 and may be regulated differently than its murine counterpart.

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Gene Transcription and Translation in Design

Volume 7: 27th International Conference on Design Theory and Methodology ◽

10.1115/detc2015-46128 ◽

2015 ◽

Author(s):

Yuemin Hou ◽

Ji Linhong

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Design Process ◽

Gene Transcription ◽

Protein Gene ◽

Developmental Process ◽

Transformation Process ◽

Whole Body ◽

Engineering Product ◽

Development Framework

An organism grows from very small to the whole body, while an engineering product is assembled from elements. An organism is formed autonomously and adaptable to his/her/its environment, while an engineering product can only execute very limited actions. The formation of a product determines its functionality. Nature is the best teacher for learning how structures are formed for specific functionality. This paper compares the design process with the developmental process of embryo and proposes a qualitative development framework that simulates the gene transcription and translation in biology. The key step in design is transforming behaviors to structures. This is a process from information to the form and it bears some similarity with the process from DNA to the protein in embryogenesis. Three basic steps are required from DNA to the protein: gene transcription, transport and protein synthesis, which is named as gene expression. Key mechanisms contributing to this transformation process are investigated and a qualitative development framework are constructed for a growth design process. Simple examples are presented for illustration of proposed methods.

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Wilms' Tumor Gene Expression in Human CD34+ Hematopoietic Progenitors During Fetal Development and Early Clonogenic Growth

Blood ◽

10.1182/blood.v89.9.3486 ◽

1997 ◽

Vol 89 (9) ◽

pp. 3486-3486 ◽

Cited By ~ 48

Author(s):

Hans D. Menssen ◽

Hans-J. Renkl ◽

Michael Entezami ◽

Eckhard Thiel

Keyword(s):

Gene Expression ◽

Fetal Development ◽

Wilms Tumor ◽

Hematopoietic Progenitors ◽

Wilms Tumor Gene ◽

Human Cd34 ◽

Clonogenic Growth ◽

Tumor Gene Expression ◽

Tumor Gene

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Regulation of Wilms' tumor gene expression by nerve growth factor and follicle-stimulating hormone in the immature mouse ovary

Fertility and Sterility ◽

10.1016/j.fertnstert.2008.07.012 ◽

2009 ◽

Vol 91 (4) ◽

pp. 1451-1454 ◽

Cited By ~ 6

Author(s):

Jaesook Roh ◽

Jeehyeon Bae ◽

Kangseok Lee ◽

Kelly Mayo ◽

Lonnie Shea ◽

...

Keyword(s):

Gene Expression ◽

Nerve Growth Factor ◽

Growth Factor ◽

Wilms Tumor ◽

Follicle Stimulating Hormone ◽

Mouse Ovary ◽

Wilms Tumor Gene ◽

Immature Mouse ◽

Tumor Gene Expression ◽

Tumor Gene

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Inhibition of cellular proliferation by the Wilms' tumor suppressor WT1 is associated with suppression of insulin-like growth factor I receptor gene expression.

Molecular and Cellular Biology ◽

10.1128/mcb.15.7.3516 ◽

1995 ◽

Vol 15 (7) ◽

pp. 3516-3522 ◽

Cited By ~ 76

Author(s):

H Werner ◽

Z Shen-Orr ◽

F J Rauscher ◽

J F Morris ◽

C T Roberts ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Tumor Suppressor ◽

Cell Line ◽

Cellular Proliferation ◽

Wilms Tumor ◽

Gene Promoter ◽

R Gene ◽

Factor I ◽

Igf I

We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells. The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA). To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression.

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