Transforming growth factor-β1 induces cell cycle arrest by activating atypical cyclin-dependent kinase 5 through up-regulation of Smad3-dependent p35 expression in human MCF10A mammary epithelial cells

2016 ◽  
Vol 472 (3) ◽  
pp. 502-507 ◽  
Author(s):  
Seong Ji Park ◽  
Sun Woo Yang ◽  
Byung-Chul Kim
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Transforming Growth Factor Β1 ◽  
Mammary Epithelial ◽  
Cyclin Dependent Kinase ◽  
Cycle Arrest ◽  
Cyclin Dependent Kinase 5

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 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.

Actions of the soy phytoestrogen genistein in models of human chronic disease: potential involvement of transforming growth factor β

2001 ◽  
Vol 29 (2) ◽  
pp. 216-222 ◽  
Author(s):  
H. Kim ◽  
J. Xu ◽  
Y. Su ◽  
H. Xia ◽  
L. Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Hormone Replacement ◽  
Transforming Growth Factor Β ◽  
Mammary Epithelial ◽  
Primate Model ◽  
Human Mammary Epithelial Cells ◽  
Human Mammary Epithelial

The structural similarity, but non-identity, between 17β-oestradiol and the soy phytoestrogen genistein suggests that the two compounds will have actions that may be identical in some target biological systems, but different in others. Epidermal growth factor (EGF)-stimulated proliferation of human mammary epithelial cells (that do not express the oestrogen receptor) was significantly suppressed at genistein concentrations (5–10μM) that are attainable physiologically. Others have shown previously that transforming growth factor β (TGFβ) has similar growth-inhibitory effects on human cells. Analysis of the conditioned medium of human mammary epithelial cells exposed to genistein plus EGF showed increased levels of TGFβ relative to those in the medium of cells exposed to EGF or genistein alone. Related experiments in a primate model of menopause demonstrated that ingestion of soy containing isoflavones was correlated with the suppression of neurodegeneration-relevant phosphorylation of the microtubule-associated protein tau, while intake of Premarin (a hormone replacement therapy that is commonly prescribed for women) was not correlated. The results discussed here indicate that genistein, and probably other related phytoestrogens, have pleiotropic actions, some of which may involve TGFβ activity.

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