Molecular mechanisms underlying progesterone-induced cytoplasmic retention of p27 in breast cancer cells

Publication date: Available online 27 June 2018Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Hui-Chen Wang, Wen-Sen LeeAbstractIt has been reported that progesterone (P4) can contribute to the aggressiveness of human breast cancers through promoting cytoplasmic localization of p27 and stimulating proliferation. However, the molecular mechanisms underlying P4-induced cytoplasmic retention of p27 are still unclear. Here, we demonstrated that P4 (12.5–100 nM) concentration-dependently increased the number of T47D and MCF-7 cells. P4 (50 nM) also time-dependently increased the levels of p27 protein. Knock-down of p27 using the small interfering RNA (siRNA) technique abolished the P4-increased cell number of T47D and MCF-7. The signaling pathway involved in the P4-promoted breast cancer cell proliferation was further investigated. Our results suggest that P4 activated the PI3K/AKT-mediated signaling, subsequently increasing phophorylation of p27 at pT198 and T157, and thereby caused cytoplasmic retention of p27 protein. In addition, P4 activated kinase-interacting stathmin (KIS), subsequently increasing phosphorylation of nuclear p27 at serine 10 (S10), and thereby caused cytoplasmic translocation of p27pS10 from the nucleus. P4 also increased the level of nuclear CDK2pT160, thereby inducing p27 phosphorylation at T187, and hence caused cytosolic translocation of p27pT187 from the nucleus. In the cytosol, both p27pS10 and p27pT187 were degra...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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In conclusion, the results indicated that overexpression of HLA-G in MCF-7 cells was induced by DNA methylation modification. The lower DNMT1 and DNMT3a and higher TET2 expression levels may be responsible for the abnormal DNA methylation of HLA-G in MCF-7. Treatment with TET inhibitor prevented aberrant HLA-G expression and DNA methylation in MCF-7. The present study may provide potential targets for novel anti-cancer drugs. PMID: 31086605 [PubMed]
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
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Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
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Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
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Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
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Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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