Deletion of the Met Tyrosine Kinase in Liver Progenitor Oval Cells Increases Sensitivity to Apoptosis in Vitro

Castillo, Gaelle del; Factor, Valentina M.; Fernández, Margarita; Álvarez-Barrientos, Alberto; Fabregat, Isabel; Thorgeirsson, Snorri S.; Sánchez, Aránzazu

doi:10.2353/ajpath.2008.070793

Cited by 32 publications

(57 citation statements)

References 50 publications

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“…We have previously described that addition of exogenous HGF resulted in an approximate 50% decrease in the TGF-β-induced apoptosis [16]. The same decrease was observed when AG1478 was present (Fig.…”

Section: Oval Cells Express Egfrsupporting

confidence: 67%

“…Met flx/flx and Met -/-oval cell lines were generated as described previously [16]. Cells were routinely maintained in DMEM supplemented with 10%FBS in a humidified incubator at 37°C and a 5% CO 2 atmosphere.…”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

“…Previously, we have reported that TGF-β induces apoptosis in oval cells and that lack of c-Met tyrosine kinase activity makes oval cells more sensitive to the pro-apoptotic effects of this cytokine [16]. To gain greater insights into the EGFR-driven antiapoptotic activity, we also tested the effect of AG1478 on TGF-β-treated oval cells.…”

Section: Oval Cells Express Egfrmentioning

confidence: 99%

“…Hence, we next tested the consequences of inhibiting the EGFR kinase on HGF-driven signalling. As seen in We have previously reported that HGF elicits mitogenic and anti-apoptotic activities in mouse oval cells [16]. To unequivocally assess whether or not EGFR kinase contributes to HGF-mediated activities in oval cells, we chose to analyze the effects of the inhibitor AG1478 on HGF-driven proliferation and survival.…”

Section: Oval Cells Express Egfrmentioning

confidence: 99%

“…Furthermore, in vivo infusion with either EGF or HGF amplifies liver progenitor expansion following liver injury and decreases cell apoptosis [15]. Recently, using a novel in vitro model of oval cell lines harboring a genetically inactivated c-met tyrosine kinase, we have demonstrated that c-Met-supported signalling plays an essential role in promoting oval cell survival but is dispensable for proliferation [16]. We have also seen that EGF elicits mitogenic activity in mouse oval cells in vitro.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

Martínez-Palacián

Castillo

Herrera

et al. 2012

Cellular Signalling

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Section: Oval Cells Express Egfrsupporting

confidence: 67%

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

Section: Oval Cells Express Egfrmentioning

confidence: 99%

Section: Oval Cells Express Egfrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

Martínez-Palacián

Castillo

Herrera

et al. 2012

Cellular Signalling

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Engineering CHO cells with an oncogenic KIT improves cells growth, resilience to stress, and productivity

Mahameed

Tirosh

2017

Biotech & Bioengineering

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An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity, and resistance to kinase inhibitors. Importantly, this onco-KIT mutant when introduced into various cell types is arrested in the endoplasmic reticulum in a constitutively active form. Here, we investigated the effect of oncogenic D816V KIT on the performance of CHO-K1 cells under conventional tissue culture growth settings and when adapted, to shaking conditions. The onco-KIT promoted global protein synthesis, elevated the expression of a secretable transgene, enhanced proliferation, and improved the overall titers of a model glycoprotein. Moreover, the expression of the onco-KIT endowed the cells with a remarkable resistance to various stress conditions. Our data suggest that the introduction of onco-KIT can serve as a strategy for improving glycoprotein biomanufacturing. Biotechnol. Bioeng. 2017;114: 2560-2570. © 2017 Wiley Periodicals, Inc.

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HSCs play a distinct role in different phases of oval cell‐mediated liver regeneration

Chen

Zhang

Zhou

et al. 2012

Cell Biochemistry & Function

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Hepatic stem cell niche plays an important role in hepatic oval cell-mediated liver regeneration. As a component of hepatic stem cell niche, the role of hepatic stellate cells (HSCs) in oval cell proliferation needs further studies. In the present study, we isolated HSCs from rats at indicated time point after partial hepatectomy (PH) in 2-acetylaminofluorene/PH oval cell proliferation model. Conditional medium (CM) from HSCs were collected to detect their effects on proliferation and the mitogen-activated protein kinase pathway activation of two oval cell lines. We found that CM collected from HSCs at early phase of liver regeneration (4 and 9 days group) contained high levels of hepatocyte growth factor (HGF) and stimulated oval cell proliferation via extracellular signal-regulated kinase and p38 pathway. CM collected from HSCs at terminal phase of liver regeneration (12 and 15 days group) contained high levels of transforming growth factor (TGF)-β1, which suppressed DNA synthesis of oval cells. The shift between these two distinct effects depended on the balance between HGF and TGF-β1 secreted by HSCs. Our study demonstrated that HSCs acted as a positive regulator at the early phase and a negative regulator at the terminal phase of the oval cell-mediated liver regeneration.

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Deletion of the Met Tyrosine Kinase in Liver Progenitor Oval Cells Increases Sensitivity to Apoptosis in Vitro

Cited by 32 publications

References 50 publications

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

Engineering CHO cells with an oncogenic KIT improves cells growth, resilience to stress, and productivity

HSCs play a distinct role in different phases of oval cell‐mediated liver regeneration

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