ArticleBrain pathology (Zurich, Switzerland)2002
Vitamin D and its analog EB1089 induce p27 accumulation and diminish association of p27 with Skp2 independent of PTEN in pituitary corticotroph cells.
Article in Brain pathology (Zurich, Switzerland), 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 36 citations in OpenAlex.
- Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Characterization of the Synergistic Inhibition ofInternational journal of molecular sciences · 2020Article
- Epidemiology and biomarker profile of pituitary adenohypophysial tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Overview of the 2017 WHO Classification of Pituitary Tumors.Endocrine pathology · 2017Review
- Genomic approaches to problems in pituitary neoplasia.Endocrine pathology · 2014Review
- Pituitary tumors: prognostic indicators.Endocrine · 2005Review
- p27Kip1 is expressed in proliferating cells in its form phosphorylated on threonine 187.BMC clinical pathology · 2005Article
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Authors and funding
3 authors at 1 institution in 2 countries.
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Abstract
Disruption of the gene for the cyclin dependent kinase inhibitor (CDKI) p27/kip1 results in pituitary corticotroph hyperplasia while diminished expression of this protein has been described in aggressive human pituitary tumors. We have previously shown that 1,25-vitamin D3 (VD) hypophosphorylates p27 and interferes with the degradation of this CDKI in thyroid carcinoma cells. In this study we investigated whether VD/EB1089 can induce p27 accumulation and cause growth arrest of pituitary corticotroph cells. VD and EB1089 exhibited a significant reduction in AtT20 corticotroph but not PRL235 lactotroph cell growth. These changes were accompanied by selective accumulation of p27 in AtT20 but not in PRL235 cells. As p27 levels are highly dependent on protein degradation, we examined the effect of VD/EB1089 on p27 association with factors that target this CDKI to the proteasome. VD/EB1089 significantly restricted the association of p27 with Skp2 as well as with cyclin dependent kinase 2 (CDK2). As the tumor suppressor and phosphatase PTEN has been implicated in p27 regulation, we tested whether the effects of VD/EB1089 on p27 accumulation in corticotrophs could be mediated through this pathway. VD/EB1089 did not appreciably alter PTEN expression. Moreover, transfection of PTEN did not influence the effect of VD on p27 accumulation in corticotrophs. We conclude that VD/EB1089 can selectively arrest pituitary corticotroph growth and induce p27 accumulation.This effect is mediated at least partially through diminished p27 association with Skp2 and with CDK2. In contrast to other cell systems, PTEN does not participate in the regulation of corticotroph p27 and is not involved in mediating the effect of VD on p27 in these cells. Our findings highlight p27 and VD analogs as targets for manipulation and drug development respectively in the treatment of inoperable corticotroph adenomas.
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