Identification of a Novel Interleukin-15 (IL-15) Transcript Isoform Generated by Alternative Splicing in Human Small Cell Lung Cancer Cell Lines

IL-15 is a cytokine promoting growth and differentiation of T, B and NK lymphocytes. By RT-PCR analysis, using primers allowing amplification of the entire IL-15 mRNA coding region, 9/11 small cell lung cancer (SCLC) cell lines displayed detectable IL-15 gene expression. In addition to the expected band sizing 524 bp, a larger band was also observed. Cloning and sequence analysis of the larger cDNA from two SCLC cell lines revealed a size of 643 hp due to the presence of additional 119 hp within the previously reported IL-15 cDNA sequence. The 119 hp sequence matched with an IL-15 genomic sequence downstream the IL-15 second coding exon and may represent a previously unreported alternative exon (exon A). The SCLC-associated IL-15 mRNA isoform has a shorter open reading frame (ORF) due to stop codons in exon A, followed by a new AUG codon. The predicted IL-15 precursor protein displays a shorter signal peptide but shares the same aminoacidic composition of mature IL-15 protein. A possible functional role of IL-15, different from 'IL-2-like' activity, in human tumours, is suggested.