The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors

• DOI: 10.1677/erc-09-0100
• Publication Date: 2009-10-07T03:49:30Z
• Authors: I Ben-Batalla; S Seoane; M Macia; T Garcia-Caballero; L O Gonzalez; F Vizoso; R Perez-Fernandez
• Keywords: 0301 basic medicine; Transcription, Genetic; Carcinoma, Ductal, Breast; Breast Neoplasms; Genes, bcl-1; Neoplasm Proteins; Prolactin; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Cell Line, Tumor; Mutagenesis, Site-Directed; NIH 3T3 Cells; Animals; Humans; Cyclin D1; Female; RNA Interference; Regular papers; RNA, Small Interfering; Promoter Regions, Genetic; Transcription Factor Pit-1; Cell Division

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.