Header

UZH-Logo

Maintenance Infos

EGF- and CPA-induced mitogenic stimuli are differentially down- regulated by TGF-beta1 in cultured rat hepatocytes


Fasciati, R (1997). EGF- and CPA-induced mitogenic stimuli are differentially down- regulated by TGF-beta1 in cultured rat hepatocytes. Carcinogenesis, 18(5):911-917.

Abstract

Down-regulation of the mitogenic activity of the rodent liver carcinogen cyproterone acetate (CPA) and of epidermal growth factor (EGF) were compared in cultured rat hepatocytes. Both hepatomitogens produce an increase in the expression of proliferating cell nuclear antigen (PCNA) and in [3H]thymidine incorporation in a dose-dependent manner. In combination, the two mitogens induced an additive mitogenic response. Concomitant exposure to the growth inhibitory cytokine transforming growth factor beta1 (TGF-beta1) resulted in a differential dose-dependent down-regulation of PCNA-expressing cells. The corresponding down-regulation of CPA-induced PCNA expression required a 3- to 5-fold higher TGF-beta1 concentration than for EGF-induced expression. In contrast, CPA-exposed hepatocytes become vulnerable to and EGF-exposed cells protected against the apoptosis-inducing activity of TGF-beta1 (>0.1 ng/ml). Under culture conditions that mimicked a pericentral-equivalent microenvironment (low oxygen tension, low glucagon concentration), PCNA expression was 3-fold lower and CPA-specific resistance was no longer detectable. It is concluded that EGF and CPA induce their growth stimuli preferentially in the periportal area of the liver but in different hepatocyte sub-populations, which differ in their down-regulation of premitotic events by TGF-beta1. At low TGF-beta1 concentrations, EGF-stimulated cells shift back into a resting cell cycle phase, whereas CPA-treated hepatocytes are eliminated by apoptosis at higher TGF-beta1 concentrations

Abstract

Down-regulation of the mitogenic activity of the rodent liver carcinogen cyproterone acetate (CPA) and of epidermal growth factor (EGF) were compared in cultured rat hepatocytes. Both hepatomitogens produce an increase in the expression of proliferating cell nuclear antigen (PCNA) and in [3H]thymidine incorporation in a dose-dependent manner. In combination, the two mitogens induced an additive mitogenic response. Concomitant exposure to the growth inhibitory cytokine transforming growth factor beta1 (TGF-beta1) resulted in a differential dose-dependent down-regulation of PCNA-expressing cells. The corresponding down-regulation of CPA-induced PCNA expression required a 3- to 5-fold higher TGF-beta1 concentration than for EGF-induced expression. In contrast, CPA-exposed hepatocytes become vulnerable to and EGF-exposed cells protected against the apoptosis-inducing activity of TGF-beta1 (>0.1 ng/ml). Under culture conditions that mimicked a pericentral-equivalent microenvironment (low oxygen tension, low glucagon concentration), PCNA expression was 3-fold lower and CPA-specific resistance was no longer detectable. It is concluded that EGF and CPA induce their growth stimuli preferentially in the periportal area of the liver but in different hepatocyte sub-populations, which differ in their down-regulation of premitotic events by TGF-beta1. At low TGF-beta1 concentrations, EGF-stimulated cells shift back into a resting cell cycle phase, whereas CPA-treated hepatocytes are eliminated by apoptosis at higher TGF-beta1 concentrations

Statistics

Citations

Dimensions.ai Metrics
9 citations in Web of Science®
7 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

10 downloads since deposited on 25 Sep 2018
6 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Cancer Research
Language:English
Date:1 May 1997
Deposited On:25 Sep 2018 14:14
Last Modified:15 Aug 2020 00:25
Publisher:Oxford University Press
ISSN:0143-3334
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/carcin/18.5.911
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093carcin185911 (Library Catalogue)

Download

Hybrid Open Access

Download PDF  'EGF- and CPA-induced mitogenic stimuli are differentially down- regulated by TGF-beta1 in cultured rat hepatocytes'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 301kB
View at publisher