Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis
Isabel Ben-Batalla, Samuel Seoane, Tomas Garcia-Caballero, Rosalia Gallego, Manuel Macia, Luis O. Gonzalez, Francisco Vizoso, Roman Perez-Fernandez
Isabel Ben-Batalla, Samuel Seoane, Tomas Garcia-Caballero, Rosalia Gallego, Manuel Macia, Luis O. Gonzalez, Francisco Vizoso, Roman Perez-Fernandez
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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 4

Subcutaneous injection of Pit-1–overexpressing MCF-7 cells in SCID mice increases tumor growth and induces EMT.

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Subcutaneous injection of Pit-1–overexpressing MCF-7 cells in SCID mice ...
(A) Seven SCID mice were subcutaneously injected with control MCF-7 cells (left flank) or MCF-7 cells stably transfected with Pit-1 expression vector (right flank). C, control cells; P, Pit-1–overexpressing MCF-7 cells. (B) Box plot of tumor growth in SCID mice, as described in A. The bottom and the top of the boxes represent the first and third quartiles (i.e., the 25th and 75th percentile, respectively), and the bands near the middle of each box represent the 50th percentile (the median). The ends of the whiskers represent the lowest and the highest values still within 1.5 interquartile range of the lower and upper quartiles, respectively. (C and D) Western blot and immunohistochemistry of Pit-1 in tumors of SCID mice injected with MCF-7 control cells stably transfected either with the pTRE2-hPit-1 expression vector or the control vector (pTRE2) at day 20. Double arrowheads in the Pit-1 immunoblot indicate 33-kDa and 31-kDa immunoreactive bands. Scale bar: 40 μm. (E) Immunohistochemistry analysis of epithelial (CK AE1-AE3, CK-19, E-cadherin, and β-catenin), mesenchymal (vimentin), and proliferation (Ki-67) markers in tumors of SCID mice injected with control or Pit-1–overexpressing MCF-7 cells. Scale bar: 25 μm.