scholarly journals Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-κB signaling pathway in FRTL thyroid cells

2008 ◽  
Vol 30 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Meng Ren ◽  
Xia Zhong ◽  
Chun-yan Ma ◽  
Ying Sun ◽  
Qing-bo Guan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Thyroid Cells ◽  
Cycle Progression

Epidermal Growth Factor Induces Cyclin D1 in Human Pancreatic Carcinoma: Evidence for a Cyclin D1–Dependent Cell Cycle Progression

Pancreas ◽  
2001 ◽  
Vol 23 (3) ◽  
pp. 280-287 ◽  
Author(s):  
Bertram Poch ◽  
Frank Gansauge ◽  
Andreas Schwarz ◽  
Thomas Seufferlein ◽  
Thomas Schnelldorfer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cyclin D1 ◽  
Pancreatic Carcinoma ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Dependent Cell ◽  
Epidermal Growth

scholarly journals Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1.

1997 ◽  
Vol 17 (7) ◽  
pp. 3850-3857 ◽  
Author(s):  
H Aktas ◽  
H Cai ◽  
G M Cooper
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Constitutive Expression ◽  
Ras Signaling ◽  
Cdk Inhibitor ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
Cell Cycle Machinery

Activation of growth factor receptors by ligand binding initiates a cascade of events leading to cell growth and division. Progression through the cell cycle is controlled by cyclin-dependent protein kinases (Cdks), but the mechanisms that link growth factor signaling to the cell cycle machinery have not been established. We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade.

scholarly journals SAT-LB135 A Novel Cytoplasmic Membrane Estrogen-Mediated Biogenic Signaling Pathway

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Richard G Pestell
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Estrogen Receptor ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Cytoplasmic Membrane ◽  
Cycle Progression ◽  
17Β Estradiol ◽  
Localized Form

Abstract The estrogen receptor α (ERα) is known to convey both genomic and extra-genomic activities. The extra-nuclear estrogen signaling pathway is thought to involve a membrane-associated estrogen receptor (ERα), which activates PI3-kinase and Akt signaling. Maximal activation of Akt requires S473 phosphorylation. The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4/6, contributing to G1-S cell-cycle progression. Herein, cyclin D1 was shown to be located in the cytoplasmic membrane of patients with inflammatory breast cancer, human diploid fibroblasts and cancer cell lines (breast, prostate). The extra-nuclear vs. nuclear E2-induced signaling pathways can be distinguished using 17β-estradiol linked to a dendrimer conjugate (EDC), which excludes estradiol from the nucleus. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1CML) was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extra-nuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). Cyclin D1CML was sufficient to induce G1-S cell-cycle progression, cellular proliferation, colony formation. In contrast with cyclin D1NL, the cyclin D1CML induced transwell migration and the velocity of cellular migration. Together these studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions. The major adjuvant therapy for the ~70% of ERα expressing human breast cancer involves anti-estrogen therapy and the ERα/PI3K/Akt complex pathway is hyperactivated in aggressive breast tumors. The non-genomic actions of E2/ERα, mediated via cyclin D1CML may provide an important additional target. References. 1. 2. Casimiro MC et al Mol Endocrinol. 2013;27(9):1415-28. Di Sante, G, Expert Rev Anticancer Ther. 2019 Jun 20:1-19.

scholarly journals Nerve Growth Factor Regulation of Cyclin D1 in PC12 Cells through a p21RASExtracellular Signal-regulated Kinase Pathway Requires Cooperative Interactions between Sp1 and Nuclear Factor-κB

2008 ◽  
Vol 19 (6) ◽  
pp. 2566-2578 ◽  
Author(s):  
Francesco Marampon ◽  
Mathew C. Casimiro ◽  
Maofu Fu ◽  
Michael J. Powell ◽  
Vladimir M. Popov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cyclin D1 ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cooperative Interactions ◽  
Kinase Pathway

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21RASpathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF induction of cyclin D1 involved cooperative interactions of extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase pathways downstream of p21RAS. NGF induced the cyclin D1 promoter via Sp1, nuclear factor-κB, and cAMP-response element/activated transcription factor sites. NGF induction via Sp1 involved the formation of a Sp1/p50/p107 complex. Cyclin D1 induction by NGF governs differentiation and neurite outgrowth in PC12 cells.

scholarly journals Regulation of the G2–M cell cycle progression by the ERK5–NFκB signaling pathway

2007 ◽  
Vol 177 (2) ◽  
pp. 253-264 ◽  
Author(s):  
Kelly Cude ◽  
Yupeng Wang ◽  
Hyun-Jung Choi ◽  
Shih-Ling Hsuan ◽  
Honglai Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cancer Biology ◽  
Cell Cycle Progression ◽  
Nuclear Factor Κb ◽  
Cyclin B1 ◽  
M Cell ◽  
Cycle Progression ◽  
Mitotic Entry ◽  
Ribosomal S6 Kinase

Elucidation of mechanisms regulating cell cycle progression is of fundamental importance for cell and cancer biology. Although several genes and signaling pathways are implicated in G1–S regulation, less is known regarding the mechanisms controlling cell cycle progression through G2 and M phases. We report that extracellular signal–regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinases, is activated at G2–M and required for timely mitotic entry. Stimulation of ERK5 activated nuclear factor κB (NFκB) through ribosomal S6 kinase 2 (RSK2)-mediated phosphorylation and degradation of IκB. Furthermore, selective inhibition of NFκB at G2–M phases substantially delayed mitotic entry and inhibited transcription of G2–M–specific genes, including cyclin B1, cyclin B2, Plk-1, and cdc25B. Moreover, inhibition of NFκB at G2–M diminished mitosis induced by constitutive activation of ERK5, providing a direct link between ERK5, NFκB, and regulation of G2–M progression. We conclude that a novel ERK5–NFκB signaling pathway plays a key role in regulation of the G2–M progression.

scholarly journals Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jodi C. Allen ◽  
Petra Seidel ◽  
Tobias Schlosser ◽  
Emma E. Ramsay ◽  
Qi Ge ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Glucocorticoid Receptor ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Platelet Derived Growth Factor ◽  
Cycle Progression ◽  
Repressive Effect ◽  
Mrna And Protein Expression

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G1 cell cycle progression—cyclin D1—in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

scholarly journals The SPARC-related Factor SMOC-2 Promotes Growth Factor-induced Cyclin D1 Expression and DNA Synthesis via Integrin-linked Kinase

2008 ◽  
Vol 19 (1) ◽  
pp. 248-261 ◽  
Author(s):  
Peijun Liu ◽  
Jining Lu ◽  
Wellington V. Cardoso ◽  
Cyrus Vaziri
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Ectopic Expression ◽  
Receptor Activation ◽  
Related Factor ◽  
Cycle Progression ◽  
Integrin Linked Kinase

Secreted modular calcium-binding protein-2 (SMOC-2) is a recently-identified SPARC-related protein of unknown function. In mRNA profiling experiments we, found that SMOC-2 expression was elevated in quiescent (G0) mouse fibroblasts and repressed after mitogenic stimulation with serum. The G0-specific expression of SMOC-2 was similar to that of platelet-derived growth factor-β receptor (PDGFβR), a major mitogenic receptor. Therefore, we tested a possible role for SMOC-2 in growth factor-induced cell cycle progression. SMOC-2 overexpression augmented DNA synthesis induced by serum and fibroblast mitogens (including PDGF-BB and basic fibroblast growth factor). Conversely, SMOC-2 ablation by using small interfering RNA attenuated DNA synthesis in response to PDGF-BB and other growth factors. Mitogen-induced expression of cyclin D1 was attenuated in SMOC-2–ablated cells, and cyclin D1-overexpressing cells were resistant to inhibition of mitogenesis after SMOC-2 ablation. Therefore, cyclin D1 is limiting for G1 progression in SMOC-2–deficient cells. SMOC-2 ablation did not inhibit PDGF-induced PDGFβR autophosphorylation or PDGF-BB–dependent activation of mitogen-activated protein kinase and Akt kinases, suggesting that SMOC-2 is dispensable for growth factor receptor activation. However, integrin-linked kinase (ILK) activity was reduced in SMOC-2–ablated cells. Ectopic expression of hyperactive ILK corrected the defective mitogenic response of SMOC-2–deficient cells. Therefore, SMOC-2 contributes to cell cycle progression by maintaining ILK activity during G1. These results identify a novel role for SMOC-2 in cell cycle control.

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