Eur J Endocrinol
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DOI: 10.1530/eje.1.01962
European Journal of Endocrinology, Vol 153, Issue 2, 335-344
Copyright © 2005 by European Society of Endocrinology
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EXPERIMENTAL STUDY

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

C Gil-Puig1, S Seoane1, M Blanco2, M Macia3, T Garcia-Caballero2, C Segura2 and R Perez-Fernandez1

1 Departments of Physiology, 2 Morphological Sciences and 3 Obstetrics and Gynecology, School of Medicine, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

(Correspondence should be addressed to R Perez-Fernandez; Email: fsropefe{at}usc.es)

Background: The transcription factor pituitary-1 (Pit-1) is mainly expressed in the pituitary gland, where it has critical roles in cell differentiation and as a transcriptional factor for GH and prolactin (PRL). It is also expressed in human extrapituitary tissues (placenta, lymphoid and haematopoietic tissues) and cell lines (human breast adenocarcinoma cells, MCF-7). Despite the widely suggested roles of GH and PRL in the progression of proliferative mammary disorders, Pit-1 expression in human mammary gland has not yet been reported.

Objective: To evaluate the expression of Pit-1 in human breast and, using the MCF-7 cell line, to investigate whether Pit-1 overexpression regulates GH expression and increases cell proliferation.

Methods: Using real-time RT-PCR, western blotting and immunohistochemistry, we evaluated the expression of Pit-1 mRNA and protein in seven normal human breasts and 14 invasive ductal mammary carcinomas. GH regulation by Pit-1 in MCF-7 cells was evaluated using RT-PCR, western blotting, ELISA and transfection assays. Cell proliferation was evaluated using bromodeoxyuridine.

Results: We found expression of Pit-1 mRNA and protein in both normal and tumorous human breast. We also found that Pit-1 mRNA levels were significantly increased in breast carcinoma compared with normal breast. In MCF-7 cells, Pit-1 overexpression increased GH mRNA and protein concentrations and significantly increased cell proliferation.

Conclusions: These findings indicate that Pit-1 is expressed in human breast, that it regulates endogenous human mammary GH secretion, and that it increases cell proliferation. This suggests that, depending on its level of expression, Pit-1 may be involved in normal mammary development, breast disorders, or both.




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