Research Article
Immunology and Cell Biology (1999) 77, 11–18; doi:10.1046/j.1440-1711.1999.00791.x
Expression of apoptotic regulatory molecules in renal cell carcinoma: Elevated expression of Fas ligand
Colleen Olive1, Catherine Cheung1, David Nicol2 and Michael C Falk1
- 1 Renal Research Laboratory, Department of Renal Medicine, Woolloongabba, Brisbane, Queensland, Australia
- 2 Department of Urology, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia
Correspondence: Dr C Olive, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Qld 4102, Australia. Email: <mdcolive@dingo.uq.edu.au>
Received 3 August 1998; Accepted 14 September 1998.
Abstract
Renal cell carcinoma (RCC) is the most common renal neoplasm. Despite being infiltrated by tumour infiltrating lymphocytes (TIL), these TIL are unable to control tumour growth in vivo, suggesting that the cytotoxic capacity of TIL against RCC is impaired, or that the tumour cells are resistant to killing and therefore escape detection by the immune system. It is postulated that the expression of apoptotic regulatory molecules in RCC favours tumour cell survival. The present study has therefore determined the expression of Fas (APO-1/CD95), Fas ligand (Fas L) and bcl-2 in these tumours. The expression of Fas, Fas L and bcl-2 mRNA transcripts was determined in RCC, normal kidney and peripheral blood by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), following RNA extraction and cDNA synthesis from tissues and cell samples. Transcript levels were measured by densitometry after Southern blot hybridization of PCR products with internal radio-labelled oligonucleotide probes; a densitometry score was assigned to each hybridizing DNA band and expressed as a ratio of the glyceraldehyde-3-phosphate dehydrogenase content. In peripheral blood, the expression of Fas L and bcl-2 transcripts was similar between patients and normal healthy individuals; however, Fas transcript expression was significantly down-regulated in the patients' versus normal peripheral blood (P = 0.026). Most interestingly, significantly up-regulated Fas L expression was observed in RCC compared to normal kidney (P = 0.041). In contrast, bcl-2 transcripts were well represented in normal kidney but markedly decreased in RCC (P = 0.021). The expression of Fas transcripts in normal kidney and RCC was variable. These data demonstrate elevated expression of Fas L transcripts in RCC, but the functional relevance of this remains to be investigated.
Keywords:
bcl-2, Fas, Fas ligand, immune escape, renal cell carcinoma

