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 2

Pit-1 induces invasive and malignant features in the noninvasive MCF-7 human breast carcinoma cell line.

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Pit-1 induces invasive and malignant features in the noninvasive MCF-7 h...
(A) Overexpression of Pit-1 (pTRE2-hPit-1) in MCF-7 cells after 8 days induces a significant (***P < 0.001) increase in cell colony formation in soft agar, with respect to that of control cells. C, control cells. Scale bar: 75 μm. (B and C) Cell motility through uncoated filters (migration) and through Matrigel-coated filters (invasion) at 48 hours in the control cells, pRc/RSV–transfected MCF-7 cells, and pRSV-hPit-1–transfected MCF-7 cells (***P < 0.001 versus control cells). Numbers represent mean ± SD. (C) Representative example of B. Cells were stained with crystal violet, visualized with microscopy, and counted. Scale bar: 100 μm. (D) Wound healing assay. The wounded areas (space indicated by arrows) were examined with microscopy at the indicated times. Scale bar: 250 μm. (E) Protein extracts of MCF-7 cells 48 hours after transfection with the empty vector (pRc/RSV) or with pRSV-hPit-1–expressing vector were prepared and tested using Western blotting for E-cadherin, Snai1, MMP-1, Pit-1, and β-actin. (F) Western blot assay showing a suppression of E-cadherin expression 72 hours after Pit-1 overexpression in MCF-7 cells. (E and F) Double arrowheads in the MMP-1 immunoblot indicate proenzyme form (top arrow) and active form (bottom arrow). Double arrowheads in Pit-1 immunoblots indicate 33-kDa and 31-kDa immunoreactive bands.