Related Experiment Video
Updated: Apr 16, 2026
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Genome-Wide Profiling of TRACK Kidneys Shows Similarity to the Human ccRCC Transcriptome
Leiping Fu1, Denise R Minton1, Tuo Zhang2
1Department of Pharmacology, Weill Cornell Medical College (WCMC) of Cornell University, New York, New York. Weill Cornell Meyer Cancer Center, Weill Cornell Medical College (WCMC) of Cornell University, New York, New York.
Unlabelled:
Renal cell carcinoma (RCC) is the most common cancer arising from the kidney in adults, with clear cell RCC (ccRCC) representing the majority of all RCCs. Expression of a human HIF1α triple-mutant (P402A, P564A, and N803A) construct in the proximal tubule cells of C57BL/6 mice [TRAnsgenic model of Cancer of the Kidney (TRACK); ref. 1] mimics the histologic changes found in early stage human ccRCC. To better understand the genomic landscape, a high-throughput sequence analysis was performed with cDNA libraries (RNAseq) derived from TRACK transgenic positive (TG(+)) kidney cortex along with human ccRCC transcripts from the Oncomine and The Cancer Genome Atlas databases. Importantly, the expression profiles of TRACK TG(+) kidneys show significant similarities with those observed in human ccRCC, including increased expression of genes involved in glycolysis and the tricarboxylic acid cycle. Some of the transcripts overexpressed in both the TRACK mouse model and human ccRCC include ANKRD37, CA9, EGLN3, HK2, NDUFA4L2, and SLC16A3. These data suggest that constitutive activation of HIF1α in kidney proximal tubule cells transcriptionally reprograms the regulation of metabolic pathways in the kidney and that HIF1α is a major contributor to the altered metabolism observed in human ccRCC.
Implications:
TRACK (GGT-HIF1αM3) kidney mRNA profiles show similarities to human ccRCC transcriptome and phenotypes associated with the Warburg effect.
Insights
The TRAnsgenic model of Cancer of the Kidney (TRACK) mouse model mimics human clear cell renal cell carcinoma (ccRCC) by showing similar gene expression, particularly in metabolic pathways. This highlights HIF1α
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Renal cell carcinoma (RCC), particularly clear cell RCC (ccRCC), is a significant adult kidney cancer.
- The TRAnsgenic model of Cancer of the Kidney (TRACK) mouse model utilizes a human HIF1α triple-mutant construct in kidney proximal tubule cells to replicate early-stage ccRCC histology.
Purpose of the Study:
- To investigate the genomic landscape of the TRACK mouse model.
- To compare the transcriptomic profiles of the TRACK mouse model with human ccRCC.
Main Methods:
- High-throughput sequence analysis (RNAseq) of cDNA libraries from TRACK transgenic positive (TG(+)) kidney cortex.
- Analysis of human ccRCC transcripts from the Oncomine and The Cancer Genome Atlas databases.
Main Results:
- TRACK TG(+) kidneys exhibit significant similarities to human ccRCC expression profiles.
- Overexpression of genes involved in glycolysis and the tricarboxylic acid cycle was observed in both TRACK TG(+) kidneys and human ccRCC.
- Specific overexpressed transcripts include ANKRD37, CA9, EGLN3, HK2, NDUFA4L2, and SLC16A3.
Conclusions:
- Constitutive HIF1α activation in kidney proximal tubule cells transcriptionally reprograms metabolic pathways.
- HIF1α plays a major role in the altered metabolism characteristic of human ccRCC.
- TRACK mouse model mRNA profiles align with human ccRCC transcriptome and Warburg effect phenotypes.
More Related Videos
05:36Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
06:29Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression
Published on: January 31, 2025
Related Concept Videos
01:20The Retinoblastoma Gene
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,...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...