A spliced isoform of interleukin 6 mRNA produced by renal cell carcinoma encodes for an interleukin 6 inhibitor.
Interleukin 6 (IL-6) is a multifunctional and pleiotropic cytokine and in renal cell carcinoma (RCC), this cytokine exerts proinflammatory, immunosuppressive and growth stimulating properties. A spliced isoform of IL-6 mRNA has been described in peripheral blood mononuclear cells and encodes for a potential protein lacking IL-6 activity. In the present study, a novel spliced form of IL-6 mRNA was found detectable in RCC cell lines, normal renal cells, but not in other tumor cells. This splicing resulted in a frameshift and the generation of multiple stop codon in the spliced IL-6 mRNA. However, two ATG of the third IL-6 exon were identified as translation initiation sites and two truncated IL-6 (tIL-6) with the expected molecular weight were recovered from transfected cell supernatant. The cDNA of a spliced form of IL-6 mRNA detected in RCC lines was cloned, and expressed in a baculovirus expression vector. The functional properties of the tIL-6 were investigated and this protein blocked IL-6 bioactivity, including mitogenic activity on tumor cells. In conclusion, this spliced form of IL-6 mRNA detected in RCC encodes for a truncated IL-6 with IL-6 antagonist properties.
Alberti
Laurent
L
Equipe Cytokine et Cancer, Unité Institut National de la Sante et de la Recherche Medicale, Centre Léon Bérard, Lyon, France, and Hôpital Edouard Herriot, Place d'Arsonval, Lyon, France.
Bachelot
Thoma
T
Duc
Adeline
A
Biota
Catherine
C
Blay
Jean Yves
JY
D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005822:Genetic Vectors; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D000093242:Interleukin-6 Inhibitors
D018076:DNA, Complementary; D015850:Interleukin-6; D020033:Protein Isoforms; D012333:RNA, Messenger; D000093242:Interleukin-6 Inhibitors