Authors: Lixin Zhang Anda Vlad Christine Milcarek Olivera J Finn
Publish Date: 2012/09/02
Volume: 62, Issue: 3, Pages: 423-435
Abstract
MUC1 is a transmembrane mucin with important functions in normal and transformed cells carried out by the extracellular domain or the cytoplasmic tail A characteristic feature of the MUC1 extracellular domain is the variable number of tandem repeats VNTR region Alternative splicing may regulate MUC1 expression and possibly function We developed an RTPCR method for efficient isolation of MUC1 mRNA isoforms that allowed us to evaluate the extent of alternative splicing of MUC1 and elucidate some of the rules that govern this process We cloned and analyzed 21 24 and 36 isoforms from human tumor cell lines HeLa MCF7 and Jurkat respectively and 16 from normal activated human T cells Among the 78 MUC1 isoforms we isolated 76 are new and different cells showed varied MUC1 expression patterns The VNTR region of exon 2 was recognized as an intron with a fixed 5′ splice site but variable 3′ splice sites We also report that the 3506 A/G SNP in exon 2 can regulate 3′ splice sites selection in intron 1 and produce different MUC1 short isoform proteins Furthermore the SNP A to G mutation was also observed in vivo during de novo tumor formation in MUC1+/−KrasG12D/+PtenloxP/loxP mice No specific functions have been associated with previously reported short isoforms We now report that one new G SNPassociated isoform MUC1/YLSP but not the A SNPassociated isoform MUC1/Y inhibits tumor growth in immunocompetent but not immunocompromised mice
Keywords: