Expression of apoptotic tumour necrosis factor receptor-associated factor, caspase recruitment domain and cell death-inducing DFF-45 effector genes in therapy-treated renal cell carcinoma.
OBJECTIVE
Dysfunction in apoptosis plays a role in development of renal cell carcinoma (RCC). This investigation aimed to identify expression of apoptosis-related genes not previously characterized in human RCC.


METHODS
The RCC ACHN cell line was treated with radiation plus interferon-alpha to induce significant apoptosis. Apoptosis RNA microarrays were used to compare control and treated RCC for apoptosis-regulatory genes with significantly altered expression (>or= twofold). Translational correlates were analysed using western blot. Immunohistochemistry of human RCC and non-cancerous kidney in tissue microarrays was also completed.


RESULTS
Several gene families, not well characterized in RCC, were significantly upregulated in RNA microarray. These were the tumour necrosis factor receptor-associated factors (TRAF1, 3 and 4), caspase recruitment domain (NOL3 and PYCARD), and cell death-inducing DFF-45 effector domain (ICAD/CAD) genes. The protein expression patterns did not always increase similarly, perhaps indicating some post-transcriptional controls needing further investigation. TRAF1 had significantly increased expression for RNA and protein (P<0.01). NOL3 had significantly decreased whole-cell protein expression (P<0.05), but had strongly localized nuclear positivity in RCC in the immunohistochemistry.


CONCLUSIONS
These newly identified RCC apoptosis genes have shown potential for improving outcome in other cancers and may prove to have the same potential in RCC with further study.
Rajandram
Retnagowri
R
Molecular and Cellular Pathology, UQCCR, The University of Queensland, Brisbane, Queensland, Australia.
Pat
Betty K
BK
Li
Jun
J
Johnson
David W
DW
Gobe
Glenda C
GC
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053468:CARD Signaling Adaptor Proteins; D002292:Carcinoma, Renal Cell / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000473:pathology* / Q000628:therapy; D008938:Mitosis; D009124:Muscle Proteins; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics*; D053449:TNF Receptor-Associated Factor 4 / Q000235:genetics*; D046888:Tissue Array Analysis
D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; C112246:NOL3 protein, human; C402202:PYCARD protein, human; D047990:TNF Receptor-Associated Factor 1; D048008:TNF Receptor-Associated Factor 3; D053449:TNF Receptor-Associated Factor 4; C090656:TRAF3 protein, human; C506367:TRAF4 protein, human; C109664:caspase-activated DNase inhibitor