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Aberrant expression of epidermal growth factor receptor and HER-2 (erbB-2) messenger RNAs in human renal cancers
M R Freeman1, R Washecka, L W Chung
1Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
Amplification, rearrangement, or overexpression of the gene for the epidermal growth factor receptor (EGFR) occurs in certain types of human neoplasia. We investigated EGFR gene structure and measured EGFR mRNA levels in human renal tumor biopsies. Seventeen renal tumors [13 renal cell carcinomas (RCCs), two Wilms' tumors, one oncocytoma, and one metastatic ganglioneuroblastoma] and their corresponding normal kidney tissues were examined for EGFR gene structural integrity by Southern blot hybridization. Twelve of these tumors (including 11 RCCs) were examined for EGFR mRNA expression levels by RNA blot hybridization. The EGFR gene was rearranged in one of 13 (8%) of the RCC specimens examined and was highly amplified in the ganglioneuroblastoma. The overall frequency of EGFR gene structure alterations in this series of renal tumors was 12%. Nine of 11 RCC specimens (82%) exhibited markedly elevated EGFR mRNA levels (approximately 2- to 6-fold). In contrast, expression of the EGFR-related protooncogene HER-2 (erbB-2) was found to be decreased in 11 RCCs and one Wilms' tumor; HER-2 gene structure, however, appeared normal in all specimens. These results indicate that overexpression of EGFR mRNA, probably due to changes in gene regulation, and underexpression of HER-2 mRNA are characteristic features of human RCC.
Insights
Epidermal growth factor receptor (EGFR) gene alterations and overexpression are common in kidney tumors, particularly renal cell carcinoma (RCC). HER-2 protooncogene expression is decreased in RCC, suggesting distinct roles in kidney cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Alterations in the epidermal growth factor receptor (EGFR) gene, including amplification, rearrangement, or overexpression, are observed in various human cancers.
- EGFR plays a crucial role in cell growth and proliferation, making its dysregulation a significant factor in neoplasia.
Purpose of the Study:
- To investigate the structural integrity of the EGFR gene and measure EGFR mRNA levels in human renal tumor biopsies.
- To determine the frequency of EGFR gene alterations and assess EGFR mRNA expression in different types of renal tumors, with a focus on renal cell carcinoma (RCC).
Main Methods:
- Southern blot hybridization was used to examine EGFR gene structural integrity in 17 renal tumors and corresponding normal kidney tissues.
- RNA blot hybridization was employed to measure EGFR mRNA expression levels in 12 of these tumors, including 11 RCCs.
Main Results:
- EGFR gene rearrangement was detected in 8% of RCC specimens, and high-level amplification was found in a ganglioneuroblastoma. Overall, 12% of renal tumors showed EGFR gene structural alterations.
- Markedly elevated EGFR mRNA levels (2- to 6-fold) were observed in 82% of RCC specimens.
- In contrast, expression of the related protooncogene HER-2 (erbB-2) was decreased in most RCCs and one Wilms' tumor, while its gene structure remained normal.
Conclusions:
- Overexpression of EGFR mRNA, likely due to altered gene regulation, is a characteristic feature of human renal cell carcinoma.
- Underexpression of HER-2 mRNA is also characteristic of human RCC, suggesting a potential reciprocal relationship or distinct roles in kidney cancer pathogenesis.
- These findings highlight the significance of EGFR and HER-2 dysregulation in the molecular landscape of renal tumors, particularly RCC.