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

Aim: 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 (≥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. Conclusion: 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.