Naslov
Signal transduction cascade during liver regeneration in mice : c-erbB2, H-ras, K-ras, c-myc

Autori
Montana, Vedrana ; Verbanac, Donatella ; Milin, Čedomila ; Radošević-Stašić, Biserka ; Pavelić, Krešimir

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Cell Signalling Mechanisms, FEBS 97 - Special Meeting / Congress Secretariat - Amsterdam : Elsevier, 1997, P6-062

Skup
FEBS 97 - Special Meeting

Mjesto i datum
Amsterdam, Nizozemska, 29.06.1997. - 03.07.1997

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
liver regeneration; oncogenes; oncoproteins; signal transduction

Sažetak
Liver regeneration after partial hepatectomy (PH) remains an exceptional model system to dissect the complex multicomponent growth regulatory signals.This compensatory growth consists of three stages: i) priming-an elevation of the protooncogenes which are known as immediate-early genes; ii) progression- made by up-regulation of delayed-early genes; iii) inhibition-synthesis of factors which are inhibitory and most likely regulate interminable growth.There are also evidence that blood-borne factors regulate the proliferative response to PH. Ligand activation of prominent hepatocyte mitogens:EGF,TGFa and HGF bind to receptors with tyrosine kinase activity and appears to play an important role in promoting hepatocyte proliferation. EGF binds to its receptor coded by c-erbB gene family, including c-erbB-2. Although c-erbB-2 does not have its own ligand, it associates with other c-erbB members of the family with ligand-binding domain forming heterodimers. Autophosphorylation of specific tyrosine residues in the cytoplasmic domain of the receptor interacts with membrane-associate Ras, product of ras protooncogene, and activates it. Down-stream Ras signal transduction cascade has several pathways. One of them terminates by c-myc, growth-regulatory transcription factor, transcribed in response to strong mitogenic stimuli.The aim of this work was to follow the appearance of some protein-products of protooncogenes: c-erbB-2, H-ras, K-ras and c-myc, involved in signal transduction pathway during 15 days period of compensatory liver growth in Balb/c mice after performed 1/3 partial hepatectomy. All the results were established by immunohistochemically staining the slices of liver tissue. The proteins were identified using specific monoclonal antibody.The obtained results showed that the accumulation of c-erbB2 occurred only during the early phase (2-8 hrs) of compensatory liver growth. H-ras and K-ras are maximally expressed between 4 and 24 hrs after PH, while c-myc appeared in 3 waves. c-myc was present immediately after PH, in the late phase (24-48 hrs), and again at the end of the process (15-th day). From the obtained data we can assume that the second peak of c-myc appearance is due to Ras-protein family pathway activation.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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