Related Experiment Videos
A pathologic link between Wilms tumor suppressor gene, WT1, and IFI16
Marianne K-H Kim1, Jacqueline M Mason, Chi-Ming Li
1Division of Hematology/Oncology, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Neoplasia (New York, N.Y.)
|January 31, 2008
Summary
The Wilms tumor gene (WT1) and interferon-inducible protein 16 (IFI16) interact to promote Wilms tumor cell survival. Targeting WT1 or IFI16 with shRNA reduced tumor cell growth, suggesting a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Wilms tumor gene (WT1) mutations are linked to heredofamilial syndromes but rare in sporadic Wilms tumors.
- Understanding WT1's role in sporadic tumors is crucial for developing targeted therapies.
Purpose of the Study:
- Identify novel WT1 target genes in Wilms tumors.
- Investigate the functional relationship between WT1 and identified target genes in tumor cell survival.
Main Methods:
- Microarray analysis comparing syndromic and sporadic Wilms tumors.
- WT1 induction experiments in Saos-2 osteosarcoma cells.
- Immunohistochemistry and co-immunoprecipitation to assess protein interactions.
- Short hairpin RNA (shRNA)-mediated knockdown studies.
Main Results:
- Interferon-inducible protein 16 (IFI16) identified as a differentially expressed gene and WT1 target.
- WT1 directly regulates IFI16 expression and promoter activity.
- WT1 and IFI16 colocalize in Wilms tumors and interact in vivo.
- IFI16 enhances WT1 transcriptional activity.
- Knockdown of either WT1 or IFI16 inhibits Wilms tumor cell growth.
Conclusions:
- IFI16 is a novel WT1 target gene involved in Wilms tumor pathogenesis.
- The WT1-IFI16 axis plays a significant role in Wilms tumor cell survival.
- Targeting the WT1-IFI16 interaction may offer a therapeutic avenue for Wilms tumors.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
02:54Canonical Wnt Signaling Pathway
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
01:41Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
01:41Non-Canonical Wnt Signaling Pathways
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...