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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Publication date: 15 August 2018Source: Life Sciences, Volume 207Author(s): Joytirmay Tripathy, Anindita Tripathy, Muthusamy Thangaraju, Mrutyunjay Suar, Selvakumar ElangovanAbstractAimsInvasion and metastasis are the main cause of mortality in breast cancer. Hence, novel therapeutic interventions with high specificity toward invasion and metastasis are necessary. α-Lipoic acid showed antiproliferative and cytotoxic effects on several cancers including breast cancer. However, the effect of lipoic acid on breast cancer metastasis remains unclear.Main methodsIn the present study, we examined the effects of lipoic acid ...
Source: Life Sciences - Category: Biology Source Type: research
In this study, we showed that IR-783 inhibits cell viability and induces mitochondrial apoptosis in human breast cancer cells. Exposure of MDA-MB-231 cells to IR-783 resulted in the loss of mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) depletion, mitochondrial permeability transition pore (mPTP) opening and cytochrome c (Cyto C) release. Furthermore, we found that IR-783 induced dynamin-related protein 1 (Drp1) translocation from the cytosol to the mitochondria, increased the expression of mitochondrial fission proteins mitochondrial fission factor (MFF) and fission-1 (Fis1), and decreased the expres...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Publication date: September 2018Source: Biomedicine &Pharmacotherapy, Volume 105Author(s): Wen-Hua Yang, Ming-Jian Ding, Guo-Zhong Cui, Meng Yang, Dian-Lu DaiAbstractDespite significant progress in the treatment of breast cancer due to advances in surgery, cytotoxic agents, and endocrine therapy, the prognosis for patients has not improved much. Accumulated evidence indicates that heterogeneous nuclear ribonucleoprotein M (hnRNPM) and Wnt/β-catenin function as tumor oncogenes in the progression of many cancers. The present study aimed to explore whether HnRNPM/β-catenin signaling molecules might serve as a ge...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
ConclusionGinsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research
Publication date: 15 August 2018Source: Life Sciences, Volume 207Author(s): Joytirmay Tripathy, Anindita Tripathy, Muthusamy Thangaraju, Mrutyunjay Suar, Selvakumar ElangovanAbstractAimsInvasion and metastasis are the main cause of mortality in breast cancer. Hence, novel therapeutic interventions with high specificity toward invasion and metastasis are necessary. α-Lipoic acid showed antiproliferative and cytotoxic effects on several cancers including breast cancer. However, the effect of lipoic acid on breast cancer metastasis remains unclear.Main methodsIn the present study, we examined the effects of lipoic acid ...
Source: Life Sciences - Category: Biology Source Type: research
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 ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
Publication date: September 2018Source: Biomedicine &Pharmacotherapy, Volume 105Author(s): Wen-Hua Yang, Ming-Jian Ding, Guo-Zhong Cui, Meng Yang, Dian-Lu DaiAbstractDespite significant progress in the treatment of breast cancer due to advances in surgery, cytotoxic agents, and endocrine therapy, the prognosis for patients has not improved much. Accumulated evidence indicates that heterogeneous nuclear ribonucleoprotein M (hnRNPM) and Wnt/β-catenin function as tumor oncogenes in the progression of many cancers. The present study aimed to explore whether HnRNPM/β-catenin signaling molecules might serve as a ge...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
ConclusionGinsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.
Source: Journal of Ginseng Research - Category: Complementary Medicine Source Type: research
Contributors : Evelyne Collignon ; Annalisa Canale ; Cl émence Al Wardi ; Martin Bizet ; Emilie Calonne ; Dedeurwaerder Sarah ; Whitney Barham ; Soizic Garaud ; Céline Naveaux ; Sophie Bouchat ; Carine Van Lint ; Karen Willard-Gallo ; Christos Sotiriou ; Agnès Noel ; François FuksSeries Type : Methylation profiling by high throughput sequencingOrganism : Homo sapiensTen eleven translocation enzymes (TET1-3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), inducing DNA demethylation and gene regulation. They are often downregulated in cancer, yet the upstream cause of this event ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : Evelyne Collignon ; Annalisa Canale ; Cl émence Al Wardi ; Martin Bizet ; Emilie Calonne ; Dedeurwaerder Sarah ; Whitney Barham ; Soizic Garaud ; Céline Naveaux ; Sophie Bouchat ; Carine Van Lint ; Karen Willard-Gallo ; Christos Sotiriou ; Agnès Noel ; François FuksSeries Type : Methylation profiling by arrayOrganism : Homo sapiensTen eleven translocation enzymes (TET1-3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), inducing DNA demethylation and gene regulation. They are often downregulated in cancer, yet the upstream cause of this event remains largely unkno...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research
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