scholarly journals The MicroRNA 424/503 Cluster Reduces CDC25A Expression during Cell Cycle Arrest Imposed by Transforming Growth Factor   in Mammary Epithelial Cells

2014 ◽  
Vol 34 (23) ◽  
pp. 4216-4231 ◽  
Author(s):  
D. Llobet-Navas ◽  
R. Rodriguez-Barrueco ◽  
J. de la Iglesia-Vicente ◽  
M. Olivan ◽  
V. Castro ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Cycle Arrest

scholarly journals Cell Cycle Arrest by Transforming Growth Factor β1 Enhances Replication of Respiratory Syncytial Virus in Lung Epithelial Cells

2009 ◽  
Vol 83 (23) ◽  
pp. 12424-12431 ◽  
Author(s):  
John D. Gibbs ◽  
Douglas M. Ornoff ◽  
Heather A. Igo ◽  
Jennifer Y. Zeng ◽  
Farhad Imani
Keyword(s):  
Cell Cycle ◽  
Respiratory Syncytial Virus ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Transforming Growth Factor ◽  
Immune Dysregulation ◽  
Cycle Arrest ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a common respiratory viral infection in children which is associated with immune dysregulation and subsequent induction and exacerbations of asthma. We recently reported that treatment of primary human epithelial cells (PHBE cells) with transforming growth factor β (TGF-β) enhanced RSV replication. Here, we report that the enhancement of RSV replication is mediated by induction of cell cycle arrest. These data were confirmed by using pharmacologic inhibitors of cell cycle progression, which significantly enhanced RSV replication. Our data also showed that RSV infection alone resulted in cell cycle arrest in A549 and PHBE cells. Interestingly, our data showed that RSV infection induced the expression of TGF-β in epithelial cells. Blocking of TGF-β with anti-TGF-β antibody or use of a specific TGF-β receptor signaling inhibitor resulted in rescue of the RSV-induced cell cycle arrest, suggesting an autocrine mechanism. Collectively, our data demonstrate that RSV regulates the cell cycle through TGF-β in order to enhance its replication. These findings identify a novel pathway for upregulation of virus replication and suggest a plausible mechanism for association of RSV with immune dysregulation and asthma.

Signaling and apoptosis differences between severe hypoxia and desferoxamine treatment of human epithelial cells

2008 ◽  
Vol 86 (5) ◽  
pp. 425-436 ◽  
Author(s):  
Adrian Harold Box ◽  
Carol Yuen ◽  
Dragana Ponjevic ◽  
Gordon H. Fick ◽  
Douglas James Demetrick
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Epithelial Cells ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Severe Hypoxia ◽  
Cycle Arrest ◽  
Induced Apoptosis

The mechanisms by which cells undergo proliferation arrest or cell death in response to hypoxia are still not completely understood. Originally, we showed that HeLa and Hep3B carcinoma cells undergo different proliferation responses in hypoxia. We now show that these 2 cell lines also have different cell death responses to severe hypoxia, with HeLa showing both cell cycle arrest and apoptosis (as early as 12 h after hypoxia treatment), and Hep3B showing resistance to both. Hypoxia-induced apoptosis in Hela was associated with decreases of both phospho-S473- and -T308-AKT and loss of AKT function, whereas Hep3B cells were resistant to hypoxia-induced apoptosis and did not lose phospho-AKT or AKT function. We then decided to test if our observations were confirmed using a hypoxia mimic, desferoxamine. Desferoxamine treatment yielded cell cycle arrest in HeLa and moderate arrest in Hep3B but, surprisingly, did not induce notable apoptosis of either cell line with up to 24 h of treatment. Hypoxia-treated normal human mammary epithelial cells also showed hypoxia-induced apoptosis. Interestingly, in these cell lines, there was a complete correlation between loss of phospho-AKT and (or) total AKT, and susceptibility to hypoxia-induced apoptosis. Our data suggests a model in which regulated loss of active AKT at a precise time point in hypoxia may be associated with apoptosis in susceptible cells.

scholarly journals FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor β1 signaling

2019 ◽  
Vol 294 (46) ◽  
pp. 17555-17569 ◽  
Author(s):  
Ichiro Kurakazu ◽  
Yukio Akasaki ◽  
Mitsumasa Hayashida ◽  
Hidetoshi Tsushima ◽  
Norio Goto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Human Mesenchymal Stem Cells ◽  
Type Ii Collagen ◽  
Transforming Growth Factor Β1 ◽  
Type Ii ◽  
Cycle Arrest

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor β1 (TGFβ1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFβ1/SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sex-determining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFβ1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9. To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNA by TGFβ1, and FOXO1 bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cell-cycle arrest during chondrogenic differentiation via TGFβ1 signaling.

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