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Differential apoptosis gene expression in pediatric tumors of the kidney
S Takamizawa1, S Okamoto, W Bishop
1Department of Surgery, University of Iowa Hospitals & Clinics, Iowa City 52242, USA.
Background/Purpose:
Apoptosis, or programmed cell death, is essential in maintaining normal homeostasis of tissues. The process of apoptosis is controlled by numerous pro- and antiapoptotic factors. Variations in expression of such factors may account for some variations in tumor behavior. This study evaluates the expression of apoptotic mRNA species in pediatric renal tumors to determine whether a pattern of differential apoptosis gene expression correlates with tumor grade and type.
Methods:
Twenty-five frozen tissue specimens were obtained from patients undergoing biopsy or resection of pediatric renal tumors before chemotherapy: Wilms' tumor stage II (WT-II, n = 4); Wilms' tumor stage III/IV (WT-III/IV, n = 4); clear cell sarcoma of the kidney stage III (CCSK, n = 2); rhabdoid tumor of the kidney stage III/IV (RTK, n = 4); and normal kidney (NK, n = 11). An RNase Protection Assay (RPA) was performed for 19 pro- and antiapoptotic mRNA species to detect and quantify expression (percentage of GAPDH expressed). Expression of specific mRNAs of interest were confirmed by Western Blot (WB).
Results:
The expression of apoptotic mRNA species varied markedly between tumors. WT-II expressed greater amounts of proapoptotic receptor mRNA than CCSK or RTK. (Fas, 17.0+/-2.7% v. 2.5+/-0.5% v. 3.3+/-0.9%; P<.02; DR5, 77.0+/-8.8% v. 13.5+/-0.5% v. 27.0+/-4.8; P<.001; TNF-R, 71.3+/-17.0% v. 21.0+/-4.0% v. 29.0+/-5.0%; P<.07, respectively). Surprisingly, antiapoptotic factors (e.g., bcl-2 and bcl-xl) were not overexpressed in poor prognostic tumors (CCSK, RTK) compared with those with good prognosis (WT). Expression of TRAIL (a ligand for DR4 and DR5) was significantly lower in CCSK and RTK than in normal kidney (9.5+/-1.5% v. 56.1+/-10.1%; P = .01).
Conclusions:
Proapoptotic receptors are expressed at greater levels in good prognostic tumors, and this finding is compatible with their clinical behavior. Knowledge of differential apoptotic gene expression is of potential value in predicting prognosis and treating such tumors with targeted ligands.
Insights
Apoptosis gene expression differs between pediatric kidney tumors. Good prognostic tumors show higher proapoptotic receptor mRNA, suggesting potential for targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Apoptosis (programmed cell death) is crucial for tissue homeostasis.
- Dysregulation of apoptotic factors can influence tumor behavior.
- Differential expression of apoptotic genes may correlate with pediatric renal tumor characteristics.
Purpose of the Study:
- To evaluate apoptotic mRNA species expression in pediatric renal tumors.
- To determine if differential apoptosis gene expression correlates with tumor grade and type.
- To investigate potential prognostic markers in pediatric kidney cancers.
Main Methods:
- Analyzed 25 pediatric renal tumor specimens (Wilms' tumor, clear cell sarcoma, rhabdoid tumor) and normal kidney tissue.
- Utilized RNase Protection Assay (RPA) for 19 pro- and antiapoptotic mRNA species.
- Confirmed mRNA expression with Western Blot (WB).
Main Results:
- Apoptotic mRNA expression varied significantly across tumor types.
- Good prognostic Wilms' tumors (WT-II) showed higher proapoptotic receptor mRNA (Fas, DR5, TNF-R) than poor prognostic tumors (CCSK, RTK).
- TRAIL ligand expression was notably lower in CCSK and RTK compared to normal kidney.
Conclusions:
- Higher proapoptotic receptor expression in favorable tumors aligns with their clinical behavior.
- Understanding differential apoptosis gene expression can aid in prognosis prediction.
- Targeted ligand therapies may be beneficial for treating pediatric renal tumors.