Expression of GHF-1 protein in mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity

Dollé, Pascal; Castrillo, José Luis; Theill, Lars E.; Deerinck, Tom; Ellisman, Mark H.; Karin, Michael

doi:10.1016/0092-8674(90)90095-v

Cited by 207 publications

(112 citation statements)

References 34 publications

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“…Mice with inactivating mutations or deletions of the Pit-1 gene fail to generate somatotropes, lactotropes and thyrotropes, and consequently exhibit anterior pituitary hypoplasia and dwarfism (6), demonstrating the importance of Pit-1 in the ontogeny of the pituitary gland. Expression of Pit-1 transcripts and protein is highly regulated, and the presence of Pit-1 protein is correlated both temporally and spatially with activation of the GH gene during pituitary development (2).…”

Section: Introductionmentioning

confidence: 99%

“…Pit-1/growth hormone (GH) factor-1 (Pit-1) is a pituitary-specific transcriptional factor that has been shown to play a critical part both in cell differentiation during organogenesis of the anterior pituitary in mammals (1,2) and as a transcriptional activator for pituitary gene transcription (3 -5). In coordinate action with additional factors, it is responsible for the specification, expansion and survival of three specific cell types (somatotropes, lactotropes and a subset of thyrotropes) during anterior pituitary development (6 -8), and for the transcriptional regulation of target promoters (GH, prolactin (PRL), b subunit of thyroidstimulating hormone (TSH), GH releasing hormone (GHRH) receptor genes, and the Pit-1 gene itself) (3, 4, 6 -10).…”

Section: Introductionmentioning

confidence: 99%

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Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Gil¹,

Seoane²,

Blanco³

et al. 2005

eur j endocrinol

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Gil¹,

Seoane²,

Blanco³

et al. 2005

eur j endocrinol

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“…GHF-1 may also be involved in the activation of the gene encoding the ␤ subunit of thyroid-stimulating hormone (22,24). All of these genes are expressed exclusively in specific cell types of the anterior pituitary, which are also the site of GHF-1 expression (11,32). In addition to its role in target gene activation, GHF-1 is required for expansion of committed somatotropes and lactotropes, which synthesize GH and PRL, respectively, during anterior pituitary development (6,24).…”

mentioning

confidence: 99%

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

Caelles

Hennemann

Karin

1995

Molecular and Cellular Biology

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GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)-and prolactin-expressing cells in the anterior pituitary. It was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA) phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain, thereby inhibiting its binding to the GH promoter. These results, however, are inconsistent with the physiological stimulation of GH production by the cAMP pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in living cells and although they stimulate the phosphorylation of GHF-1, the inhibitory phosphoacceptor site within the homeodomain is not affected. Instead, this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result, GHF-1 DNA binding activity is transiently inhibited during the M phase. This activity is regained once cells enter G 1 , a phase during which GHF-1 phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA binding Ser-382. As this site is conserved in all POU proteins, it appears that all members of this group are similarly regulated. A specific kinase activity distinct in its substrate specificity and susceptibility to inhibitors from the Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This novel activity could be involved in regulating the DNA binding activity of all POU proteins in a cell cycle-dependent manner.

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“…Pit-1 is critical for cell differentiation during organogenesis of the anterior pituitary gland in mammals (11) and as a transcriptional activator for pituitary gene transcription (i.e., transcription of prolactin [PRL], growth hormone [GH], and Pit-1 itself) (12)(13)(14). Mice with inactivating mutations or deletions of the Pit1 gene fail to generate somatotropes, lactotropes, and thyrotropes and consequently exhibit anterior pituitary hypoplasia and dwarfism (15), demonstrating the importance of Pit-1 in the ontogeny of the pituitary gland.…”

Section: Introductionmentioning

confidence: 99%

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

Ben-Batalla¹,

Seoane²,

García‐Caballero³

et al. 2010

J. Clin. Invest.

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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.

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Expression of GHF-1 protein in mouse pituitaries correlates both temporally and spatially with the onset of growth hormone gene activity

Cited by 207 publications

References 34 publications

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation

M-Phase-Specific Phosphorylation of the POU Transcription Factor GHF-1 by a Cell Cycle-Regulated Protein Kinase Inhibits DNA Binding

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

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