Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary transcription factor-1 (Pit-1) plays a key role in cell differentiation during organogenesis of the anterior pituitary, and as a transcriptional activator for the pituitary GH and prolactin genes. However, Pit-1 is also expressed in nonpituitary cell types and tissues. In breast tumors, Pit-1 mRNA and protein levels are increased with respect to normal breast, and in MCF-7 human breast adenocarcinoma cells, Pit-1 increases GH secretion and cell proliferation. We report here that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] administration to MCF-7 cells induces a significant decrease in Pit-1 mRNA and protein levels. By deletion analyses, we mapped a region (located between -147 and -171 bp from the transcription start site of the Pit-1 gene) that is sufficient for the repressive response to 1,25-(OH)2D3. Gel mobility shift and chromatin immunoprecipitation assays confirmed the direct interaction between the vitamin D receptor (VDR) as homodimer (without the retinoid X receptor), and the Pit-1 promoter, supporting the view that Pit-1 is a direct transcriptional target of VDR. Our data also indicate that recruitment of histone deacetylase 1 is involved in this repressive effect. This ligand-dependent Pit-1 gene inhibition by VDR in the absence of the retinoid X receptor seems to indicate a new mechanism of transcriptional repression by 1,25-(OH)2D3.
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PMID:The vitamin D receptor represses transcription of the pituitary transcription factor Pit-1 gene without involvement of the retinoid X receptor. 1632 98

Human pituitary tumor transforming gene (hPTTG1) was recently identified as a protooncogene, which is a regulator of the cell cycle, as a homolog of yeast securin and a transcriptional activator of several angiogenic factors. Here we examined the relationships of hPTTG1 expression with cell proliferation, expression of the angiogenic factor, VEGF (vascular endothelial growth factor), and numbers of the blood vessels in the normal and/or adenomatous pituitary. With the exception of TSHoma, the expression of hPTTG1 was significantly higher in pituitary adenomas than in the normal pituitary gland. The cell proliferation activity was higher in pituitary adenomas than in the normal pituitary. Pituitary cell proliferation was significantly correlated with the level of hPTTG1 expression in the normal pituitary tissue, but there was no such correlation in the adenomas. The significant correlation of hPTTG1 with the VEGF expression and the numbers of the blood vessels was elucidated in pituitary adenomas. It is particularly noteworthy that immunohistochemical double staining indicated co-localization of VEGF in many hPTTG1-positive tumor cells. In conclusion, higher levels of hPTTG1 expression contribute to the pathobiology of pituitary adenomas by promoting angiogenesis rather than by activating cell proliferation, whereas hPTTG1 expression is related to mitotic activity in the normal pituitary gland.
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PMID:PTTG overexpression is correlated with angiogenesis in human pituitary adenomas. 1715 47