Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation.
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.
Gil-Puig
C
C
Department of Physiology, University of Santiago de Compostela, Spain.
Seoane
S
S
Blanco
M
M
Macia
M
M
Garcia-Caballero
T
T
Segura
C
C
Perez-Fernandez
R
R
D001940:Breast / Q000254:growth & development / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D012333:RNA, Messenger; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I