Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.
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.
To understand further if cytokine-gene transfection of RCC could alter certain cellular properties that are associated with the invasive and metastatic potentials of tumor, the authors characterized six cell lines that produce IL-2 and/or IFN-alpha in their expression of intercellular adhesion molecule-1 (ICAM-1) and CD44; binding affinity to extracellular matrix (ECM) components (fibronectin, laminin, type IV collagen, and vitronectin); and preference in forming homotypic aggregation and mRNA levels of c-myc, epidermal growth factor receptor (EGF-R), tumor transforming growth factor-beta (TGF-beta) and type IV collagenase.
The results demonstrate that in renal cell carcinomas a significant relationship exists between resistance-related proteins, such as P-170, GST-pi, or Topo II, and proto-oncogenes, such as c-fos, c-erbB1, and c-neu.
We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters.
Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC.
Requirement for the von Hippel-Lindau tumor suppressor gene for functional epidermal growth factor receptor blockade by monoclonal antibody C225 in renal cell carcinoma.
In patients, anti-EGFR agents can be given safely at doses that fully inhibit receptor signaling, and single-agent activity has been observed against a variety of tumor types, including colon carcinoma, non-small-cell lung cancer, head and neck cancer, ovarian carcinoma, and renal cell carcinoma.
The observed downregulation of LRIG1 and increased EGFR/LRIG1 ratios are consistent with LRIG1 being a suppressor of oncogenesis in RCC by counteracting the tumour-promoting properties of EGFR.
Here, we determined if a Her-2/Her-1 inhibitor (PKI-166) can enhance the tumor-suppressive effect of Cx32 in Caki-2 cells from human renal cell carcinoma.
Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non-small-cell lung cancer (NSCLC) and renal cell carcinomas.
These data identify EGFR as a critical determinant of HIF-2alpha-dependent tumorigenesis and show at the molecular level that EGFR remains a credible target for therapeutic strategies against VHL-/- renal carcinoma.
Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.