Transcriptional regulation of pim-1 by prolactin: independence of a requirement for Jak2/Stat signaling.
Lactogen-dependent Nb2 cell lines have been widely employed to investigate signaling mechanisms coupled to prolactin receptor (PRLR)-stimulated transcription of hormone-responsive genes. We previously reported that PRL rapidly induced expression of the immediate-early protooncogene, pim-1. In the present report, we describe experiments conducted to evaluate PRL-stimulated transcription of pim-1 as well as potential PRLR-linked signaling mechanisms leading to promoter activation. Results from promoter/reporter experiments and electrophoretic mobility gel shift analysis indicated that two elements (distal element, -427 to -336 bp, and proximal element, -104 to -1 bp) positively regulated PRL-stimulated pim-1 promoter activity while it appeared to be repressed by factor binding to a NF-1 half site located between these positive elements. Deletion of gamma-interferon activation sequences did not reduce the effect of PRL to activate the promoter. Results from pharmacological antagonism of several signaling mechanisms indicated that PRLR activation of the pim-1 promoter reflected contributions from the ras-MAPK and PI-3 kinase pathways. Together these observations suggest that PRLR stimulation of pim-1 transcription occurs independently of a requirement for signaling through a Jak2/Stat mechanism.
Buckley
A R
AR
College of Pharmacy and Department of Molecular and Cellular Physiology, University of Cincinnati Medical Center, 3223 Eden Avenue, P.O. Box 670004, Cincinnati, OH 45267-0004, USA. arthur.buckley@uc.edu
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D053614:Janus Kinase 2; D011388:Prolactin / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1; D051381:Rats; D011981:Receptors, Prolactin / Q000502:physiology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D007371:Interferon-gamma; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; C496637:Pim1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1