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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Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Short Research Communication Source Type: research
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Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 621. Lymphoma-Genetic/Epigenetic Biology Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
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Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
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Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research
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Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
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Authors: de Oca AC, Valle ER, Hernández MCR, Rojano EA, Hernández SR, Vázquez MJF, Wejebe JEM, Basurto AMC, Moctezuma IV, Basurto JC Abstract N-(2'-Hydroxyphenyl)-2-propylpentanamide (OH-VPA) is a valproic acid (VPA) derivative with improved antiproliferative activity toward breast cancer (MCF-7, MDA-MB-231, and SKBr3) and human cervical cancer cell lines (HeLa) compared to that of VPA. However, the pharmacological mechanism of OH-VPA activity remains unknown. High-mobility group box 1 (HMGB1) is an important enzyme that is highly expressed in tumor cells and has a subcellular localization that...
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