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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
BIGH3 is overexpressed in clear cell renal cell carcinoma
Masanori Yamanaka1, Fumihiro Kimura, Yutaka Kagata
1Department of Urology, National Defense Medical College, Saitama 359-8513, Japan.
Abstract:
To identify new target marker genes in renal cell carcinoma (RCC), we compared the gene expression profiles of clear cell RCC (cc-RCC) and normal kidney tissue using serial analysis of gene expression. Our results revealed that the transforming growth factor beta induced 68 kDa protein (TGF-betaI: beta ig-h3 (BIGH3), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor beta1 (TGF-beta1) genes are up-regulated in cc-RCC. To further assess the role of BIGH3 in RCC, we investigated the mRNA expression levels of BIGH3, TGFbeta1, PAI-1 and also of TGF-beta1 related genes in 53 RCC and 30 normal kidney tissues by quantitative real-time RT-PCR (QRT-PCR). We further determined the BIGH3 protein levels in 52 cc-RCC paraffin-embedded tissue samples by immunohistochemistry. BIGH3 mRNA was found to be highly overexpressed in cc-RCC compared with normal tissues with an average ratio of 27. The mRNA levels of TGF-beta1 and PAI-1 were also detected at significantly elevated levels in these cancers. Immunohistochemical analysis of BIGH3 also revealed strong staining in the majority of the cc-RCC samples. In addition, the up-regulation of BIGH3 and PAI-1 was found to correlate with the clinicopathological parameters associated with a poorer patient outcome, whereas TGF-beta1 expression was determined to be unrelated to cancer progression. Strong BIGH3 staining thus tended to be associated with a poor prognosis. BIGH3 was also induced in some RCC cell lines by TGF-beta1 stimulation and this correlated well with PAI-1 up-regulation, suggesting that these enhancements are regulated by a similar mechanism in these tumors.
Insights
New research identifies key genes, including beta ig-h3 (BIGH3) and plasminogen activator inhibitor-1 (PAI-1), as significantly upregulated in clear cell renal cell carcinoma (cc-RCC), potentially serving as new diagnostic markers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) is a significant health concern, and identifying novel molecular markers is crucial for improved diagnosis and prognosis.
- Understanding the gene expression profiles in clear cell RCC (cc-RCC) can reveal potential therapeutic targets and biomarkers.
Purpose of the Study:
- To identify novel target marker genes in renal cell carcinoma (RCC) by comparing gene expression profiles.
- To investigate the role of beta ig-h3 (BIGH3) in RCC and its correlation with other transforming growth factor beta (TGF-beta) related genes.
Main Methods:
- Serial analysis of gene expression was used to compare gene expression profiles between cc-RCC and normal kidney tissue.
- Quantitative real-time RT-PCR (QRT-PCR) was employed to measure mRNA expression levels of BIGH3, TGF-beta1, and PAI-1.
- Immunohistochemistry was performed to determine BIGH3 protein levels in cc-RCC tissue samples.
Main Results:
- Transforming growth factor beta induced 68 kDa protein (BIGH3), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor beta1 (TGF-beta1) genes were found to be upregulated in cc-RCC.
- BIGH3 mRNA was highly overexpressed in cc-RCC (average ratio of 27), with significantly elevated levels of TGF-beta1 and PAI-1 mRNA also observed.
- Strong BIGH3 protein staining was prevalent in cc-RCC samples, and its upregulation correlated with poorer patient outcomes and cancer progression.
Conclusions:
- BIGH3 and PAI-1 are significantly upregulated in cc-RCC and may serve as valuable prognostic markers.
- The observed upregulation of BIGH3 and PAI-1 appears to be regulated by a similar mechanism, potentially involving TGF-beta1 stimulation.
- Further research into BIGH3 as a therapeutic target could lead to improved management strategies for renal cell carcinoma.
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