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

Abstract

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. 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. 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. 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.