scholarly journals A Mathematical Model Quantifies Proliferation and Motility Effects of TGF-β on Cancer Cells

2009 ◽  
Vol 10 (1) ◽  
pp. 71-83 ◽  
Author(s):  
Shizhen Emily Wang ◽  
Peter Hinow ◽  
Nicole Bryce ◽  
Alissa M. Weaver ◽  
Lourdes Estrada ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Motility ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Kolmogorov Equation ◽  
Human Mammary Epithelial

Transforming growth factor (TGF)-β is known to have properties of both a tumour suppressor and a tumour promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell–cell adhesion. Coupling mathematical modelling and experiments, we investigate the growth and motility of oncogene-expressing human mammary epithelial cells under exposure to TGF-β. We use a version of the well-known Fisher–Kolmogorov equation, and prescribe a procedure for its parametrisation. We quantify the simultaneous effects of TGF-β to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF-β treated cellsin vitro, TGF-β increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.

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.

Regulation of parathyroid hormone-related peptide production in normal human mammary epithelial cells in vitro

1994 ◽  
Vol 267 (3) ◽  
pp. C723-C730 ◽  
Author(s):  
M. Sebag ◽  
J. Henderson ◽  
D. Goltzman ◽  
R. Kremer
Keyword(s):  
Parathyroid Hormone ◽  
Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Igf I ◽  
Human Mammary Epithelial ◽  
Pthrp Expression ◽  
Normal Human ◽  
Parathyroid Hormone Related Peptide

We have examined the expression and production of parathyroid hormone-related peptide (PTHRP) in primary cultures of normal human mammary epithelial cells (HMEC) derived from nonlactating breast tissue. In response to growth factors such as insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor (EGF), immunoreactive PTHRP was released into conditioned medium, and PTHRP mRNA rapidly increased. In contrast, hydrocortisone and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited these effects in a dose-dependent manner. Addition of prolactin (PRL) in the presence or absence of insulin, IGF-I, or EGF did not influence PTHRP production during the time course studied. To investigate whether these factors were acting at the transcriptional level, we performed nuclear run-on assays and demonstrated that IGF-I increased PTHRP gene transcription whereas hydrocortisone and 1,25(OH)2D3 inhibited this effect. These studies therefore demonstrate that IGF-I, EGF, 1,25(OH)2D3, and hydrocortisone modulate PTHRP expression in HMEC and that these effects occur in part at the level of gene transcription. Additionally, PRL, a known stimulator of PTHRP expression in vivo, has no effect in this in vitro model.

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