The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors.
The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research.
Ben-Batalla
I
I
Department of Physiology, School of Medicine, University Clinical Hospital, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Seoane
S
S
Macia
M
M
Garcia-Caballero
T
T
Gonzalez
L O
LO
Vizoso
F
F
Perez-Fernandez
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019940:Genes, bcl-1; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells / Q000187:drug effects; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011388:Prolactin / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D050817:Transcription Factor Pit-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
C530104:CCND1 protein, human; D009363:Neoplasm Proteins; C494187:POU1F1 protein, human; D034741:RNA, Small Interfering; D050817:Transcription Factor Pit-1; D019938:Cyclin D1; D011388:Prolactin