Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy.
AuthorsRomero-Gallo J, Sozmen EG, Chytil A, Russell WE, Whitehead R, Parks WT, Holdren MS, Her MF, Gautam S, Magnuson M, Moses HL, Grady WM,
JournalOncogene
PubMed ID15735717
The transforming growth factor beta (TGF-beta) signaling pathway, which is activated by the TGF-beta receptor complex consisting of type I and type II TGF-beta receptors (TGFBR1 and TGFBR2), regulates cell growth and death. TGF-beta and components of its signaling pathway, particularly TGFBR2, have been implicated as tumor suppressor genes and ... More
Smad7 abrogates transforming growth factor-beta1-mediated growth inhibition in COLO-357 cells through functional inactivation of the retinoblastoma protein.
AuthorsBoyer Arnold N, Korc M,
JournalJ Biol Chem
PubMed ID15811853
'Smad7 is overexpressed in 50% of human pancreatic cancers. COLO-357 pancreatic cancer cells engineered to overexpress Smad7 are resistant to the actions of transforming growth factor-beta1 (TGF-beta1) with respect to growth inhibition and cisplatin-induced apoptosis but not with respect to modulation of gene expression. To delineate the mechanisms underlying these ... More
Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines.
AuthorsTian F, DaCosta Byfield S, Parks WT, Yoo S, Felici A, Tang B, Piek E, Wakefield LM, Roberts AB,
JournalCancer Res
PubMed ID14678987
'The role of transforming growth factor beta in breast cancer is controversial with tumor suppressor and pro-oncogenic activities having been demonstrated. To address whether the same or different signal transduction pathways mediate these opposing activities, we manipulated the Smad2/3 signaling pathway in cells of common origin but differing degrees of ... More
Differential effects of fluticasone on extracellular matrix production by airway and parenchymal fibroblasts in severe COPD.
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal repair in the lung resulting in airway obstruction associated with emphysema and peripheral airway fibrosis. Because the presence and degree of airways disease and emphysema varies between COPD patients, this may explain the heterogeneity in the response to treatment. It is ... More
BMP-7 opposes TGF-beta1-mediated collagen induction in mouse pulmonary myofibroblasts through Id2.
AuthorsIzumi N, Mizuguchi S, Inagaki Y, Saika S, Kawada N, Nakajima Y, Inoue K, Suehiro S, Friedman SL, Ikeda K,
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID16126788
Mesenchymal cells, primarily fibroblasts and myofibroblasts, are the principal matrix-producing cells during pulmonary fibrogenesis. Transforming growth factor (TGF)-beta signaling plays an important role in stimulating the expression of type I collagen of these cells. Bone morphogenetic protein (BMP)-7, a member of the TGF-beta superfamily, has been reported to oppose the ... More
Repression of bone morphogenetic protein and activin-inducible transcription by Evi-1.
AuthorsAlliston T, Ko TC, Cao Y, Liang YY, Feng XH, Chang C, Derynck R,
JournalJ Biol Chem
PubMed ID15849193
Smads, key effectors of transforming growth factor (TGF)-beta, activin, and bone morphogenetic protein (BMP) signaling, regulate gene expression and interact with coactivators and corepressors that modulate Smad activity. The corepressor Evi-1 exerts its oncogenic effects by repressing TGF-beta/Smad3-mediated transcription, thereby blocking TGF-beta-induced growth arrest. Because Evi-1 interacts with the highly ... More
Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1 in human skin fibroblasts.
AuthorsQuan T, He T, Voorhees JJ, Fisher GJ,
JournalJ Biol Chem
PubMed ID15579469
Smad7 functions as an endogenous negative regulator of transforming growth factor-beta (TGF-beta)/SMAD signaling. The TGF-beta/SMAD pathway is a major regulator of collagen production in connective tissue. Reduced expression of SMAD7 has been reported in TGF-beta-mediated fibrotic diseases, characterized by overproduction of collagen. Solar ultraviolet (UV) irradiation reduces collagen production by ... More
Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro.
AuthorsBrown KA, Aakre ME, Gorska AE, Price JO, Eltom SE, Pietenpol JA, Moses HL,
JournalBreast Cancer Res
PubMed ID15084245
Transforming growth factor (TGF)-beta1 is proposed to inhibit the growth of epithelial cells in early tumorigenesis, and to promote tumor cell motility and invasion in the later stages of carcinogenesis through the induction of an epithelial to mesenchymal transition (EMT). EMT is a multistep process that is characterized by changes ... More
Cellular response to hypoxia involves signaling via Smad proteins.
AuthorsZhang H, Akman HO, Smith EL, Zhao J, Murphy-Ullrich JE, Batuman OA,
JournalBlood
PubMed ID12411310
The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream effectors, Smad proteins (Smads), to associate with DNA. ... More