Expression of apoptotic regulatory molecules in renal cell carcinoma: Elevated expression of Fas ligand

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 o f TIL against RCC is impaired, or that the tumour cells are resistant to ki lling and therefore escape detection by the immune system. It is postulated that the expression of apoptotic regulatory molecules in RCC favours tumou r 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 ex pression of Fas, Fas L and bcl-2 mRNA transcripts was determined in RCC, no rmal kidney and peripheral blood by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), following RNA extraction and cDNA synth esis from tissues and cell samples. Transcript levels were measured by dens itometry after Southern blot hybridization of PCR products with internal ra dio-labelled oligonucleotide probes; a densitometry score was assigned to e ach hybridizing DNA band and expressed as a ratio of the glyceraldehyde-3-p hosphate dehydrogenase content. In peripheral blood, the expression of Fas L and bcl-2 transcripts was similar between patients and normal healthy ind ividuals; however, Fas transcript expression was significantly down-regulat ed in the patients' versus normal peripheral blood (P = 0.026). Most intere stingly, significantly up-regulated Fas L expression was observed in RCC co mpared to normal kidney (P = 0.041). In contrast, bcl-2 transcripts were we ll represented in normal kidney but markedly decreased in RCC (P = 0.021). The expression of Fas transcripts in normal kidney and RCC was variable. Th ese data demonstrate elevated expression of Fas L transcripts in RCC, but t he functional relevance of this remains to be investigated.