ArticleJournal of cellular physiology2010
Constitutive activation of the mitogen-activated protein kinase pathway impairs vitamin D signaling in human prostate epithelial cells.
Article in Journal of cellular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Vitamin D Receptor in Cancer: Biological Functions, Mechanistic Insights, and Clinical Relevance.Cancer management and research · 2026Review
- The Potential of Vitamin D and Epigallocatechin Gallate (EGCG) for the Treatment of Uterine Fibroids: Evidence From In Vitro to Clinical Studies.Molecular nutrition & food research · 2025Review
- Phosphorylation of RXRα mediates the effect of JNK to suppress hepatic FGF21 expression and promote metabolic syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Vitamin D and Hypoxia: Points of Interplay in Cancer.Cancers · 2022Review
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- Article
- Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPTCancer prevention research (Philadelphia, Pa.) · 2019Article
- Exploring vitamin D metabolism and function in cancer.Experimental & molecular medicine · 2018Review
- Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.The Journal of steroid biochemistry and molecular biology · 2017Article
- Phosphorylation of Human Retinoid X Receptor α at Serine 260 Impairs Its Subcellular Localization, Receptor Interaction, Nuclear Mobility, and 1α,25-Dihydroxyvitamin D3-dependent DNA Binding in Ras-transformed Keratinocytes.The Journal of biological chemistry · 2017Article
- Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype.Oncotarget · 2016Article
- Gene Signatures of 1,25-Dihydroxyvitamin D3 Exposure in Normal and Transformed Mammary Cells.Journal of cellular biochemistry · 2015Article
- The effect of 1,25 dihydroxyvitamin D3 treatment on the mRNA levels of β catenin target genes in mice with colonic inactivation of both APC alleles.The Journal of steroid biochemistry and molecular biology · 2015Review
- Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects.Proteins · 2015Article
- Genetic variants in the vitamin D pathway and breast cancer disease-free survival.Carcinogenesis · 2013Article
- Article
- MKP-1 is essential for canonical vitamin D-induced signaling through nuclear import and regulates RANKL expression and function.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Cellular and molecular effects of vitamin D on carcinogenesis.Archives of biochemistry and biophysics · 2012Review
- Vitamin D and cancer: a review of molecular mechanisms.The Biochemical journal · 2012Review
- Vitamin D3: a helpful immuno-modulator.Immunology · 2011Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We studied the effect of prolonged activation of mitogen-activated protein kinase (MAPK) signaling on 1,25 dihydroxyvitamin D (1,25(OH)(2)D(3)) action in the immortalized human prostate epithelial cell line RWPE1 and its Ki-Ras transformed clone RWPE2. 1,25(OH)(2)D(3)-treatment caused growth arrest and induced gene expression in both cell lines but the response was blunted in RWPE2 cells. Vitamin D receptor (VDR) levels were lower in RWPE2 cells but VDR over-expression did not increase vitamin-D-mediated gene transcription in either cell line. In contrast, MAPK inhibition restored normal vitamin D transcriptional responses in RWPE2 cells and MAPK activation with constitutively active MEK1R4F reduced vitamin-D-regulated transcription in RWPE1 cells. 1,25(OH)(2)D(3)-mediated transcription depends upon the VDR and its heterodimeric partner the retinoid X receptor (RXR) so we studied whether changes in the VDR-RXR transcription complex occur in response to MAPK activation. Mutation of putative phosphorylation sites in the activation function 1 (AF-1) domain (S32A, T82A) of RXRalpha restored 1,25(OH)(2)D(3)-mediated transactivation in RWPE2 cells. Mammalian two-hybrid and co-immunoprecipitation assays revealed a vitamin-D-independent interaction between steroid receptor co-activator-1 (SRC-1) and RXRalpha that was reduced by MAPK activation and was restored in RWPE2 cells by mutating S32 and T82 in the RXRalpha AF-1 domain. Our data show that a common contributor to cancer development, prolonged activation of MAPK signaling, impairs 1,25(OH)(2)D(3)-mediated transcription in prostate epithelial cells. This is due in part to the phosphorylation of critical amino acids in the RXRalpha AF-1 domain and impaired co-activator recruitment.
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