scholarly journals Transforming growth factor-β receptor III downregulation in prostate cancer: is inhibin B a tumor suppressor in prostate?

2007 ◽  
Vol 39 (5) ◽  
pp. 329-332 ◽  
Author(s):  
Nima Sharifi ◽  
Robert J Lechleider ◽  
William L Farrar
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Invasion And Metastasis ◽  
Dual Roles ◽  
Growth Inhibitory ◽  
Β Receptor

AbstractThe transforming growth factor-β (TGF-β) pathway plays dual roles in cancer, inhibiting epithelial cell growth under normal physiologic conditions, but promoting invasion and metastasis once growth inhibitory responses are lost. Two recent papers show that TGF-β receptor III is the most common TGF-β pathway component downregulated in prostate cancer. Here, we discuss the implications of these findings and what it may mean about the biology of this disease.

scholarly journals The Intracellular Form of Notch Blocks Transforming Growth Factor β-Mediated Growth Arrest in Mv1Lu Epithelial Cells

2003 ◽  
Vol 23 (18) ◽  
pp. 6694-6701 ◽  
Author(s):  
Prakash Rao ◽  
Tom Kadesch
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Transforming Growth Factor ◽  
Cell Cycle Control ◽  
Transforming Growth Factor Β ◽  
Cell Fate Decisions ◽  
Growth Inhibitory

ABSTRACT Notch signaling influences a variety of cell fate decisions during development, and constitutive activation of the pathway can provoke unbridled cell growth and cancer. The mechanisms by which Notch affects cell growth are not well established. We describe here a novel link between Notch and cell cycle control. We found that Mv1Lu epithelial cells harboring an oncogenic form of Notch (NICD) are resistant to the cell cycle-inhibitory effects of transforming growth factor β (TGF-β). NICD did not affect TGF-β signaling per se but blocked induction of the Cdk inhibitor p15INK4B. c-Myc, whose down-regulation by TGF-β is required for p15INK4B induction, remained elevated in the NICD-expressing cells. c-Myc expression was also maintained in low serum, indicating that Notch's effects on c-Myc are not specific to TGF-β. Our results are consistent with a model in which a strong Notch signal indirectly deregulates c-Myc expression and thereby renders Mv1Lu epithelial cells resistant to growth-inhibitory signals.

scholarly journals The type III transforming growth factor-β receptor inhibits proliferation, migration, and adhesion in human myeloma cells

2011 ◽  
Vol 22 (9) ◽  
pp. 1463-1472 ◽  
Author(s):  
Kathleen E. Lambert ◽  
Huang Huang ◽  
Karthikeyan Mythreye ◽  
Gerard C. Blobe
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Adhesion ◽  
Growth Factor ◽  
Cell Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Myeloma Cell ◽  
Myeloma Cells ◽  
Β Receptor

Transforming growth factor-β (TGF-β) plays an important role in regulating hematopoiesis, inhibiting proliferation while stimulating differentiation when appropriate. We previously demonstrated that the type III TGF-β receptor (TβRIII, or betaglycan) serves as a novel suppressor of cancer progression in epithelial tumors; however, its role in hematologic malignancies is unknown. Here we demonstrate that TβRIII protein expression is decreased or lost in the majority of human multiple myeloma specimens. Functionally, restoring TβRIII expression in myeloma cells significantly inhibited cell growth, proliferation, and motility, largely independent of its ligand presentation role. In a reciprocal fashion, shRNA-mediated silencing of endogenous TβRIII expression enhanced cell growth, proliferation, and motility. Although apoptosis was not affected, TβRIII inhibited proliferation through induction of the cyclin-dependent kinase inhibitors p21 and p27. TβRIII further regulated myeloma cell adhesion, increasing homotypic myeloma cell adhesion while decreasing myeloma heterotropic adhesion to bone marrow stromal cells. Mechanistically, live cell imaging of myeloma and stroma cell cocultures revealed that TβRIII-mediated inhibition of heterotropic adhesion was associated with decreased duration of myeloma/bone marrow stromal cell interaction. These results suggest that loss of TβRIII expression during multiple myeloma progression contributes to disease progression through its functional effects on increased cell growth, proliferation, motility, and adhesion.

scholarly journals The Type III Transforming Growth Factor-β Receptor as a Novel Tumor Suppressor Gene in Prostate Cancer

2007 ◽  
Vol 67 (3) ◽  
pp. 1090-1098 ◽  
Author(s):  
Ryan S. Turley ◽  
Elizabeth C. Finger ◽  
Nadine Hempel ◽  
Tam How ◽  
Timothy A. Fields ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Suppressor Gene ◽  
Type Iii ◽  
Β Receptor
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