scholarly journals Localization of Transforming Growth Factor-β1 and Type II Receptor in Developing Normal Human Prostate and Carcinoma Tissues

1998 ◽  
Vol 46 (3) ◽  
pp. 379-388 ◽  
Author(s):  
Michael J. Gerdes ◽  
Melinda Larsen ◽  
Lauren McBride ◽  
Truong D. Dang ◽  
Bing Lu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Prostate Carcinoma ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Carcinoma Cells ◽  
Human Prostate ◽  
Type Ii ◽  
Normal Prostate ◽  
Normal Human

Transforming growth factor-β1 (TGF-β1) is implicated in prostate development, and elevated expression of TGF-β1 has been correlated with prostate carcinogenesis. In this study, cell type specificity of TGF-β1 and TGF-β receptor Type II (RcII) protein expression was determined by immunocytochemistry in human normal prostate and compared to prostate carcinoma tissues. Heterogeneous localization patterns of LAP-TGF-β1 (TGF-β1 precursor) and RcII were observed in both epithelial and mesenchymal cells in fetal prostate, with LAP-TGF-β1 localizing to more basal epithelial cells. Homogeneity of LAP-TGF-β1 staining was increased in neonatal, prepubertal, and adult prostate, with elevated immunoreac-tivity noted in epithelial acini relative to stromal tissue for both LAP-TGF-β1 and RcII proteins. In stromal tissues, RcII cell localization exhibited staining patterns nearly identical to smooth muscle α-actin. In prostate carcinoma, LAP-TGF-β1 localized to carcinoma cells with an increased staining heterogeneity relative to normal prostate. In contrast to normal epithelial cells, carcinoma epithelial cells exhibited low to nondetectable RcII staining. Stromal cell staining patterns for LAP-TGF-β1 and RcII in carcinoma, however, were identical to those of normal prostate stromal cells. These studies implicate both epithelial and stromal cells as sites of TGF-β1 synthesis and RcII localization in the developing and adult normal human prostate. In addition, these data indicate a loss of epithelial expression of RcII concurrent with altered LAP-TGF-β1 expression in human prostate carcinoma cells.

scholarly journals Mechanisms of Transforming Growth Factor-β Receptor Endocytosis and Intracellular Sorting Differ between Fibroblasts and Epithelial Cells

2001 ◽  
Vol 12 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Jules J.E. Doré ◽  
Diying Yao ◽  
Maryanne Edens ◽  
Nandor Garamszegi ◽  
Elizabeth L. Sholl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Transforming Growth Factor ◽  
Point Mutations ◽  
Type I ◽  
Receptor Complex ◽  
Type Ii ◽  
Down Regulation ◽  
Β Receptor

Transforming growth factor-βs (TGF-β) are multifunctional proteins capable of either stimulating or inhibiting mitosis, depending on the cell type. These diverse cellular responses are caused by stimulating a single receptor complex composed of type I and type II receptors. Using a chimeric receptor model where the granulocyte/monocyte colony-stimulating factor receptor ligand binding domains are fused to the transmembrane and cytoplasmic signaling domains of the TGF-β type I and II receptors, we wished to describe the role(s) of specific amino acid residues in regulating ligand-mediated endocytosis and signaling in fibroblasts and epithelial cells. Specific point mutations were introduced at Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II receptor. Mutation of either Y182 or Y249, residues within two putative consensus tyrosine-based internalization motifs, had no effect on endocytosis or signaling. This is in contrast to mutation of T200 to valine, which resulted in ablation of signaling in both cell types, while only abolishing receptor down-regulation in fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial cells constitutively internalize and recycle the TGF-β receptor complex back to the plasma membrane. The data indicate fundamental differences between mesenchymal and epithelial cells in endocytic sorting and suggest that ligand binding diverts heteromeric receptors from the default recycling pool to a pathway mediating receptor down-regulation and signaling.

Effect of transforming growth factor-β on calcium homeostasis in prostate carcinoma cells

2003 ◽  
Vol 304 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Zemfira Z Gizatullina ◽  
Eva Grapengiesser ◽  
Irina G Shabalina ◽  
Jan Nedergaard ◽  
Carl-Henrik Heldin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Calcium Homeostasis ◽  
Prostate Carcinoma ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Carcinoma Cells

scholarly journals Protein tyrosine phosphatase-α amplifies transforming growth factor-β-dependent profibrotic signaling in lung fibroblasts

2020 ◽  
Vol 319 (2) ◽  
pp. L294-L311 ◽  
Author(s):  
Yael Aschner ◽  
Meghan Nelson ◽  
Matthew Brenner ◽  
Helen Roybal ◽  
Keriann Beke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Protein Tyrosine Phosphatase ◽  
Transforming Growth Factor ◽  
Tyrosine Phosphatase ◽  
Transforming Growth Factor Β ◽  
Lung Fibroblasts ◽  
Type Ii ◽  
Wild Type

Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal, fibrosing lung disease for which treatment remains suboptimal. Fibrogenic cytokines, including transforming growth factor-β (TGF-β), are central to its pathogenesis. Protein tyrosine phosphatase-α (PTPα) has emerged as a key regulator of fibrogenic signaling in fibroblasts. We have reported that mice globally deficient in PTPα ( Ptpra−/−) were protected from experimental pulmonary fibrosis, in part via alterations in TGF-β signaling. The goal of this study was to determine the lung cell types and mechanisms by which PTPα controls fibrogenic pathways and whether these pathways are relevant to human disease. Immunohistochemical analysis of lungs from patients with IPF revealed that PTPα was highly expressed by mesenchymal cells in fibroblastic foci and by airway and alveolar epithelial cells. To determine whether PTPα promotes profibrotic signaling pathways in lung fibroblasts and/or epithelial cells, we generated mice with conditional (floxed) Ptpra alleles ( Ptpraf/f). These mice were crossed with Dermo1-Cre or with Sftpc-CreERT2 mice to delete Ptpra in mesenchymal cells and alveolar type II cells, respectively. Dermo1-Cre/ Ptpraf/f mice were protected from bleomycin-induced pulmonary fibrosis, whereas Sftpc-CreERT2 /Ptpraf/f mice developed pulmonary fibrosis equivalent to controls. Both canonical and noncanonical TGF-β signaling and downstream TGF-β-induced fibrogenic responses were attenuated in isolated Ptpra−/− compared with wild-type fibroblasts. Furthermore, TGF-β-induced tyrosine phosphorylation of TGF-β type II receptor and of PTPα were attenuated in Ptpra−/− compared with wild-type fibroblasts. The phenotype of cells genetically deficient in PTPα was recapitulated with the use of a Src inhibitor. These findings suggest that PTPα amplifies profibrotic TGF-β-dependent pathway signaling in lung fibroblasts.

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