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.
Andria
M L
ML
Department of Pharmacology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Reem
G H
GH
D001665:Binding Sites / Q000235:genetics; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000502:physiology*; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
D051821:Lymphoid Enhancer-Binding Factor 1; D018808:Transcription Factor AP-1; D051176:beta Catenin; D011388:Prolactin; D000242:Cyclic AMP