Journal Article

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

R Fasciati and P Maier

in Carcinogenesis

Volume 18, issue 5, pages 911-917
Published in print May 1997 | ISSN: 0143-3334
Published online May 1997 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/18.5.911
EGF- and CPA-induced mitogenic stimuli are differentially down-regulated by TGF-beta1 in cultured rat hepatocytes.

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

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.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.