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Immunogold analysis of antioxidant enzymes in common renal cancers
T D Oberley1, J M Sempf, L W Oberley
1Pathology and Laboratory Medicine Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
Abstract:
Immunogold studies of normal human kidney and common human kidney cancers were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase, and glutathione S-transferases and their subunits. Normal tissue adjacent to human renal tumors had the same antioxidant enzyme immunoreactive protein profiles as normal human kidney, thus establishing that the presence of tumor does not alter the levels of antioxidant enzyme immunoreactive proteins in adjacent kidney tissue. Levels of immunoreactive protein for antioxidant enzymes were determined in four common types of malignant renal cancer. In general, tumors had low levels of antioxidant enzymes; however, certain histologic types of renal tumors had high levels of immunoreactive protein for glutathione S-transferase subunits, which could affect their susceptibility to chemotherapy. Studies of transitional carcinoma of the renal pelvis were especially informative since it was possible to compare levels of antioxidant enzyme immunoreactive protein with adjacent normal transitional epithelium; the majority of antibodies resulted in lower levels of immunoreactive protein in transitional cell carcinoma than in adjacent normal transitional epithelium. Our results are discussed in relation to the response of renal tumors to therapy.
Insights
Kidney cancer cells generally show low levels of antioxidant enzymes. However, specific tumor types exhibit high glutathione S-transferase levels, potentially impacting chemotherapy response.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Antioxidant enzymes play crucial roles in cellular defense against oxidative stress.
- Dysregulation of antioxidant enzymes is implicated in various cancers, including kidney cancer.
- Understanding these enzyme levels is vital for predicting cancer progression and treatment outcomes.
Purpose of the Study:
- To investigate the expression profiles of key antioxidant enzymes in normal kidney tissue and common renal cell carcinomas.
- To determine if tumor presence affects antioxidant enzyme levels in adjacent normal kidney tissue.
- To correlate antioxidant enzyme expression with specific renal tumor histology and potential chemotherapy susceptibility.
Main Methods:
- Immunogold labeling was employed to detect antioxidant enzymes, including superoxide dismutases (SODs), catalase, glutathione peroxidase (GPx), and glutathione S-transferases (GSTs) and their subunits.
- Analysis was performed on normal human kidney tissue, adjacent non-tumorous kidney tissue, and four common types of malignant renal cancers.
- Specific focus was placed on transitional cell carcinoma of the renal pelvis for direct comparison with adjacent normal epithelium.
Main Results:
- Adjacent normal kidney tissue exhibited consistent antioxidant enzyme profiles, unaffected by the presence of tumors.
- Most renal cancer types generally displayed reduced levels of antioxidant enzymes.
- Elevated levels of glutathione S-transferase subunits were observed in specific renal tumor subtypes, suggesting a potential role in chemotherapy resistance.
- Transitional cell carcinomas showed significantly lower levels of most antioxidant enzymes compared to adjacent normal transitional epithelium.
Conclusions:
- Renal cell carcinomas generally exhibit diminished antioxidant enzyme activity, with notable exceptions in GST subunit expression.
- Specific antioxidant enzyme profiles, particularly GSTs, may serve as predictive biomarkers for chemotherapy response in kidney cancer.
- Further research is warranted to elucidate the precise mechanisms and therapeutic implications of altered antioxidant enzyme levels in renal malignancies.