Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

Resistance to cancer treatments in renal cell carcinomas: discovering novel apoptotic pathways

  • Ms Retnagowri Rajandram, Molecular and Cellular Pathology, University of Queensland, Australia
  • Betty Pat, Conjoint Renal Laboratory, Queensland Health Pathology Service, Australia
  • Dr Jun Li, Molecular and Cellular Pathology, University of Queensland, Australia
  • Ms Christine Percy, Molecular and Cellular Pathology, University of Queensland, Australia
  • Dr David Vesey, Renal Medicine, Princess Alexandra Hospital, Australia
  • Prof David Johnson, Renal Medicine, Princess Alexandra Hospital, Australia
  • A/Prof Glenda Gobe, University of Queensland, Australia

    • Purpose: Renal cell carcinomas (RCCs) are resistant to cancer therapies in part by a lack of induced apoptosis. This project aimed to identify an RCC cell line in which apoptosis could be induced to such a level that the altered pathways might be analysed, and then use microarray to describe apoptosis-regulating genes that were significantly different in the apoptotic RCC versus its control.
    Methods: Two RCC cell lines (ACHN and SN12K-1) were treated with IFN-α (500IU/mL), radiotherapy (20Gy) or dual therapy of these treatments. Controls had "sham" treatment. Apoptosis was quantified at 24 and 48hrs. ACHN treated with dual therapy for 24hrs had a moderate but significant increase in apoptosis over controls (4.91±0.44% v. 1.44±0.15%) (p<0.05) and were used further for microarray assay. Microarrays (N=3; 112 apoptosis-related genes) were done using RNA extracted from treated and control ACHN and analysed for alterations of minimum 2-fold in transcripts.
    Results/Conclusions: 40 genes had upregulated and one had down-regulated 2-fold transcripts in treated cells. Bcl-2, Bax and p53 were significantly up-regulated in the array and subsequent protein analysis (Western immunoblots) showed close correlation with alterations in RNA transcript. A search of the literature revealed three gene families were novel in treated RCCs: the TNF receptor-associated factor, caspase recruitment domain, and cell death-inducing DFF-45 effector domain families. These may be worthy of further study as their modulation may attain a better level of apoptosis in treated RCCs. Their value as biomarkers needs further study.

    Conference Organiser - ICMS Pty Ltd