Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.
The Pit-1 transcription factor (also know as POU1F1) plays a critical role in cell differentiation during organogenesis of the anterior pituitary in mammals and is a transcriptional activator for pituitary gene transcription. Increased expression of Pit-1 has been reported in human tumorigenic breast cells. Here, we found that Pit-1 overexpression or knockdown in human breast cancer cell lines induced profound phenotypic changes in the expression of proteins involved in cell proliferation, apoptosis, and invasion. Some of these protumorigenic effects of Pit-1 were mediated by upregulation of Snai1, an inductor of the epithelial-mesenchymal transition. In immunodeficient mice, Pit-1 overexpression induced tumoral growth and promoted metastasis in lung. In patients with invasive ductal carcinoma of the breast and node-positive tumor, high expression of Pit-1 was significantly correlated with Snai1 positivity. Notably, in these patients elevated expression of Pit-1 was significantly and independently associated with the occurrence of distant metastasis. These findings suggest that Pit-1 could help to make a more accurate prognosis in patients with node-positive breast cancer and may represent a new therapeutic target.
Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Isabel
I
Ben-Batalla
Samuel
S
Seoane
Tomas
T
Garcia-Caballero
Rosalia
R
Gallego
Manuel
M
Macia
Luis O
LO
Gonzalez
Francisco
F
Vizoso
Roman
R
Perez-Fernandez
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D050817:Transcription Factor Pit-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014410:Tumor Stem Cell Assay
C494187:POU1F1 protein, human; D034741:RNA, Small Interfering; D050817:Transcription Factor Pit-1