Prolactin expression is induced in Jurkat T-cells by beta-catenin LEF-1, AP-1 and cAMP

Prolactin (PRL) in humans is produced in the pituitary as well as in extra-pituitary sites. A proximal promoter that requires the Pit-1 transcription factor controls pituitary PRL expression, whereas a distal (upstream) promoter located at 5.8 kb upstream of the pituitary start site regulates extra-pituitary PRL synthesis. We have previously reported that cAMP regulates PRL transcription in Jurkat lymphocytes in part through a cAMP responsive element. Here we demonstrate that additional PRL regulatory elements corresponding to LEF-l and AP-1 transcription factor binding sites appear important for PRL expression, since factor binding by EMSA and reporter gene expression are reduced when these sites are deleted or mutated. Interestingly, over-expression of a constitutively active form of beta-catenin increases PRL expression of Jurkat cells. This effect occurs through both LEF-dependent and -independent pathways. Our studies identify the distal PRL promoter as a target for beta-catenin, and reveal novel pathways regulating extra-pituitary PRL expression.