Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis
Isabel Ben-Batalla, … , Francisco Vizoso, Roman Perez-Fernandez
Isabel Ben-Batalla, … , Francisco Vizoso, Roman Perez-Fernandez
Published November 8, 2010
Citation Information: J Clin Invest. 2010;120(12):4289-4302. https://doi.org/10.1172/JCI42015.
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Research Article Oncology

Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis

Abstract

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.

Authors

Isabel Ben-Batalla, Samuel Seoane, Tomas Garcia-Caballero, Rosalia Gallego, Manuel Macia, Luis O. Gonzalez, Francisco Vizoso, Roman Perez-Fernandez

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Figure 8

Orthotopic injection of Pit-1–overexpressing MCF-7 cells in SCID mice induces metastasis in lung.

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Orthotopic injection of Pit-1–overexpressing MCF-7 cells in SCID mice in...
(A) Schematic representation of experimental induction of metastasis. At day 0, eleven SCID mice were injected with MCF-7 cells (controls) and twelve SCID mice were injected with MCF-7 cells stably transfected with Pit-1–overexpressing vector into the second mammary fad pat. At day 21, animals were anesthetized and breast tumors were resected. On day 47, mice were sacrificed and lungs were removed for analysis. Nine out of twelve SCID mice injected with MCF-7 cells overexpressing Pit-1 showed micrometastasis in lung. Two micrometastasis were observed in mice (n = 11) injected with control MCF-7 cells. (B) Representative example of micrometastasis in lung. H&E staining and immunopositivity for vimentin, CK-7, and CK-19. Scale bar: 40 μm.