Regulated Transformation of Mammary Epithelial Cells by Transforming Growth Factor-Beta 1

2002 ◽  
Author(s):  
Neil A. Bhowmick ◽  
Harold Moses
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Growth Factor Beta

scholarly journals Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

1997 ◽  
Vol 17 (5) ◽  
pp. 2458-2467 ◽  
Author(s):  
C Sandhu ◽  
J Garbe ◽  
N Bhattacharya ◽  
J Daksis ◽  
C H Pan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Cyclin D1 ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Tgf Beta ◽  
Human Mammary Epithelial ◽  
Growth Factor Beta

The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited.

scholarly journals Neoplastic transformation of mouse mammary epithelial cells by deregulated myc expression.

1990 ◽  
Vol 1 (11) ◽  
pp. 863-872 ◽  
Author(s):  
N T Telang ◽  
M P Osborne ◽  
L A Sweterlitsch ◽  
R Narayanan
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Constitutive Expression ◽  
Neoplastic Transformation ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Dependent Growth

A spontaneously immortalized, nontumorigenic mouse mammary epithelial cell line (MMEC) was transfected with an activated myc construct by electroporation. Constitutive expression of myc in MMEC resulted in anchorage independence in soft agar and tumorigenicity in nude mice. The myc-expressing MMEC showed higher saturation density, faster growth rate, and partial abrogation of serum-derived growth factor(s) requirement compared with parent MMEC. Epidermal growth factor or transforming growth factor alpha stimulated the anchorage-independent growth, but not the anchorage-dependent growth, of MMEC-myc cells. Type 1 transforming growth factor beta, on the other hand, inhibited both the anchorage-independent and anchorage-dependent growth of MMEC-myc cells. These results demonstrate that deregulated expression of myc results in neoplastic transformation iin mammary epithelial cells. Accompanying the transformation is altered sensitivity to polypeptide growth factors.

Interaction of epidermal growth factor and transforming growth factor beta in human prostatic epithelial cells in culture

The Prostate ◽  
1992 ◽  
Vol 21 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Debra M. Sutkowski ◽  
Chau-Jye Fong ◽  
Julia A. Sensibar ◽  
Alfred W. Rademaker ◽  
Edward R. Sherwood ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cells In Culture ◽  
Epidermal Growth ◽  
Growth Factor Beta

Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells

1993 ◽  
Vol 264 (4) ◽  
pp. F623-F628 ◽  
Author(s):  
F. Law ◽  
R. Rizzoli ◽  
J. P. Bonjour
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Renal Epithelial Cells ◽  
Pi Transport ◽  
Sodium Dependent ◽  
Growth Factor Beta

The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.

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