Specific effects of Lef-1 splice variants on the regulation of gene expression in pancreatic cancer cells
Cell Communication and Signaling volume 7, Article number: A32 (2009)
The lymphoid enhancer factor (Lef-1) belongs to the nuclear transducers of canonical Wnt-signalling in embryogenesis and cancer. Lef-1 acts, in cooperation with beta-catenin, as a context-dependent transcriptional activator or repressor thereby influencing multiple cellular functions such as proliferation, differentiation and migration.
Here we report an increased Lef-1 expression in human pancreatic cancer, which correlates with advanced tumour stages. As demonstrated by RT-PCR analysis, pancreatic carcinoma exhibit two different transcripts present in pancreatic carcinomas. One transcript was identified as the full length Lef-1 (Lef-1 FL), whereas the second, shorter transcript, lacked exon VI (Lef-1 exon VI) compared to the published sequence. Comparative analysis of these two Lef-1 variants revealed different cellular effects after transient expression in pancreatic carcinoma cells. Forced expression of Lef-1 exon VI in pancreatic carcinoma cells inhibited E-cadherin expression and resulted in reduced cellular aggregation and increased cell migration compared to cells expressing full length Lef-1. Expression of Lef-1 FL, but not the newly identified Lef-1 exon VI, induced expression of the cell cycle regulating proteins c-myc and cyclin D1 and resulted in enhanced cell proliferation.
Thus, our findings implicate that expression of alternatively spliced isoforms of Lef-1 are involved in the determination of proliferative or migratory characteristics of pancreatic carcinoma cells.
About this article
Cite this article
Jesse, S., Giehl, K., König, A. et al. Specific effects of Lef-1 splice variants on the regulation of gene expression in pancreatic cancer cells. Cell Commun Signal 7 (Suppl 1), A32 (2009). https://doi.org/10.1186/1478-811X-7-S1-A32