Adenovirus-mediated Transfer of a Truncated Transforming Growth Factor-β (TGF-β) Type II Receptor Completely and Specifically Abolishes Diverse Signaling by TGF-β in Vascular Wall Cells in Primary Culture

Yamamoto, H.; Ueno, Hikaru; Ooshima, Akira; Takeshita, Akira

doi:10.1074/jbc.271.27.16253

Cited by 84 publications

(76 citation statements)

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“…However, our ®ndings are in agreement with several previous reports. In Mv1Lu cells expression of a truncated TbRII or a mutant TbRI that lacks the juxtamembrane region preceding the GS domain does not attenuate TGF-b1 mediated induction of PAI-I (Yamamoto et al, 1996;Saitoh et al, 1996). None- Figure 6 E ects of Smad7 on PAI-I induction and 3TP-luciferase activity.…”

Section: Discussionmentioning

confidence: 99%

“…Data are expressed as mean+s.e.mean of three independent experiments. *P50.05 theless, these cells are resistant to the antiproliferative e ects of TGF-b1 (Yamamoto et al, 1996;Saitoh et al, 1996). Furthermore, transient overexpression of a Smad3 protein in which the three C-terminal serines have been replaced by aspartic acid blocks the antiproliferative e ects of TGF-b1 in Mv1Lu cells, while still allowing for activation of PAI-I transcription (Liu et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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The TGF-β signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer

et al. 1999

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Transforming growth factor-beta (TGF-b) signaling is dependent on the heterodimerization of the type II TGFb receptor (TbRII) with the type I TGF-b receptor (TbRI). Activated TbRI then mediates TGF-b signals by inducing the phosphorylation of Smad2 and/or Smad3, which separately hetetorodimerize with Smad4 and translocate to the nucleus. Phosphorylation of Smad2/ Smad3 by activated TbRI is inhibited by two newly discovered members of the Smad family, Smad6 and Smad7. We now report that Smad7 mRNA levels are increased in human pancreatic cancer by comparison with the normal pancreas, and that by in situ hybridization, Smad7 is over-expressed in the cancer cells within the tumor mass. Stable transfection of COLO-357 human pancreatic cancer cells with a fulllength Smad7 construct leads to complete loss of the growth inhibitory response to TGF-b1, without altering TGF-b1-mediated induction of PAI-I. Furthermore, Smad7 transfected COLO-357 cells display enhanced anchorage-independent growth and accelerated growth in nude mice. These ®ndings point to a previously unrecognized mechanism for selective suppression of TGF-b-mediated growth inhibition in cancer cells that allows for continued activation of the PAI-I promoter by TGF-b1, which may act to enhance the tumorigenicity of certain cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The TGF-β signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer

et al. 1999

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“…[21][22][23][24][25] Briefly, a cDNA coding for human wild-type p53 (kindly provided by Dr Vogelstein, Johns Hopkins Oncology Center, Program in Human Genetics, Baltimore, MD, USA) was placed into a cassette cosmid vector, pAdexCA1w (provided by Dr Saito, University of Tokyo), under a CA promoter comprising a cytomegalovirus enhancer and chicken ␤-actin promoter (pAdex1w/p53). A recombinant adenovirus was constructed by in vitro homologous recombination in 293 cells using pAdex1w/p53 and the adenovirus DNA-terminal protein complex.…”

Section: Preparation Of Adenoviral Vectorsmentioning

confidence: 99%

The levels of integrin αvβ5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells

Takayama¹,

Ueno

Pei³

et al. 1998

Gene Ther

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Adenovirus-mediated transfer of growth-inhibiting moldependent on the infection efficiency. Growth inhibition ecules, such as p53, shows promise as an effective was induced in all cell lines tested following infection with method of suppressing the growth of cancer cells. As the an adenovirus containing p53, regardless of the genetic basis for in vivo studies, we examined transfection status of their endogenous p53 provided a sufficient efficiency using 15 human lung cancer cell lines that differ amount of p53 protein was expressed. Our results (1) conin their endogenous p53 status. When infected with an firm that the examination of the susceptibility of target canadenovirus expressing bacterial ␤-galactosidase, the difcer cells to an adenovirus is important when considering ferent cell lines showed different levels of ␤-galactosidase performing adenovirus-mediated gene transfer and for evaactivity. We found a correlation between the level of inteluating its therapeutic effects; and (2) suggest that the grin ␣ v ␤5, which is thought to be an adherence receptor quantification of integrin ␣ v ␤5 may be a good way of prefor adenoviruses, and the expression level of the transdicting the susceptibility of cells to adenoviral vectors. ferred gene, suggesting that gene expression is largely

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“…16,17,26,27 AdCALacZ was purified by ultracentrifugation through a CsCl 2 gradient followed by extensive dialysis. The titer of the virus stock was assessed by a plaque formation assay using 293 cells and expressed as plaque formation units (p.f.u.).…”

Section: Adenoviral Vectormentioning

confidence: 99%

“…The electroretinographical evaluations were performed as previously described. 17,26 The rats were anesthetized with an intraperitoneal injection of 15 ml/g body weight of saline solution containing katamine (1 mg/ml), myoblock (0.4 mg/ml), and urethane (40 mg/ml). Both pupils were dilated with mydrin (2.5% phenylephrine HCl and 0.5% tropicamide content; Santen, Osaka, Japan), and the animals were placed on a heating pad.…”

Section: Electroretinograms (Ergs)mentioning

confidence: 99%

A vitrectomy improves the transfection efficiency of adenoviral vector-mediated gene transfer to Müller cells

et al. 1998

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The neural retina is a logical target of gene therapy for highest degree of gene expression was obtained by various ocular diseases. We developed a new gene delivmethods A (23.2% of total retinal area) and C (19.8%), ery method to the neural retina using an adenoviral vector while the lowest degree was obtained by method B (8.9%). with a high degree of gene transfection efficiency and lessThe inflammation was observed in all eyes and the value functional damage. An adenoviral vector bearing the lacZ of inflammation was quantified as the average inflammagene (AdCALacZ) was injected into the eyes of adult Wistory cell number in each microscopic field (cells per fields). tar rats after an SF 6 compression gas vitrectomy and left A moderate degree of inflammation was induced by for 30 min followed by washing with balanced salt solution methods B (28.3 cells per field) and C (27.5 cells per field) (BSS) (method A). Three other methods, comprising a simand a minimal degree of inflammation was induced by ple intravitreal injection (method B), an intravitreal injection method A (11.2 cells per field). We evaluated the retinal after an SF6 compression gas vitrectomy (method C) or a function by measuring an electroretinogram (ERG). The subretinal injection (method D), were also studied. The amplitudes of the ERG were depressed in all eyes treated gene expression was examined 6 days after the AdCAwith AdCALacZ. This depression was manifested most by LacZ injection. An immunohistochemical study for antimethods B and C, and least by method A. The deteriovimentin, antiglial fibrillary acidic protein and anti S100 ration in the ERG findings seemed to correlate with the protein antibodies showed the neural retinal cells (Mü ller intensity of inflammation. Our study showed that an intravicells) to be primarily transfected by methods A, B and C, treal injection with an adenoviral vector can transfer the while only a few cells were transfected by method D. The genes to the neural retinal cells and therefore a vitrectomy expression of ␤-galactosidase was visualized by X-gal and the subsequent removal of the adenoviral vector, can staining and the positive areas on each hemiflat mount thus significantly improve the transfection efficiency and specimen were measured by an image analyzer and then also reduce the degree of functional damage. were adopted as a value of gene transfer efficiency. The

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Adenovirus-mediated Transfer of a Truncated Transforming Growth Factor-β (TGF-β) Type II Receptor Completely and Specifically Abolishes Diverse Signaling by TGF-β in Vascular Wall Cells in Primary Culture

Abstract: We constructed an adenoviral vector expressing a mutated human type II transforming growth factor-␤ (TGF-␤) receptor that was truncated of its kinase domain (AdexCAT␤TR) and examined whether this truncated receptor could abolish signaling by TGF-␤ using

Cited by 84 publications

References 46 publications

The TGF-β signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer

The TGF-β signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer

The levels of integrin αvβ5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells

A vitrectomy improves the transfection efficiency of adenoviral vector-mediated gene transfer to Müller cells

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