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Differential intrac...
Differential intracellular signalling induced by TGF-beta in rat adult hepatocytes and hepatoma cells : implications in liver carcinogenesis.
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- Caja, Laia (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab
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Ortiz, Conrad (author)
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Bertran, Esther (author)
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Murillo, Miguel M (author)
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Miró-Obradors, M Jesús (author)
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Palacios, Evangelina (author)
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Fabregat, Isabel (author)
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(creator_code:org_t)
- Elsevier BV, 2007
- 2007
- English.
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In: Cellular Signalling. - : Elsevier BV. - 0898-6568 .- 1873-3913. ; 19:4, s. 683-94
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- The transforming growth factor-beta (TGF-beta) regulates hepatocyte growth, inhibiting proliferation and inducing apoptosis. Indeed, escaping from the TGF-beta suppressor actions might be a prerequisite for liver tumour progression. In this work we show that TGF-beta plays a dual role in regulating apoptosis in FaO rat hepatoma cells, since, in addition to its pro-apoptotic effect, TGF-beta also activates survival signals, such as AKT, the epidermal growth factor receptor (EGFR) being required for its activation. TGF-beta induces the expression of the EGFR ligands transforming growth factor-alpha (TGF-alpha) and heparin-binding EGF-like growth factor (HB-EGF) and induces intracellular re-localization of the EGFR. Cells that overcome the apoptotic effects of TGF-beta undergo morphological changes reminiscent of an epithelial-mesenchymal transition (EMT) process. In contrast, TGF-beta does not activate AKT in adult hepatocytes, which correlates with lack of EGFR transactivation and no response to EGFR inhibitors. Although TGF-beta induces TGF-alpha and HB-EGF in adult hepatocytes, these cells show very low expression of TACE/ADAM 17 (TNF-alpha converting enzyme), which is required for EGFR ligand proteolysis and activation. Furthermore, adult hepatocytes do not undergo EMT processes in response to TGF-beta, which might be due, at least in part, to the fact that F-actin re-organization induced by TGF-beta in FaO cells require the EGFR pathway. Finally, results indicate that EGFR transactivation does not block TGF-beta-induced cell cycle arrest in FaO cells, but must be interfering with the pro-apoptotic signalling. In conclusion, TGF-beta is a suppressor factor for adult quiescent hepatocytes, but not for hepatoma cells, where it plays a dual role, both suppressing and promoting carcinogenesis.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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