The induction of hepatoma cell apoptosis by c-myc requires zinc and
occurs in the absence of dna fragmentation.
Xu, Jun, Yang Xu, Quynh Nguyen, Phyllis M. Novikoff, and Mark J.
Czaja.
Departments of Medicine and Pathology and the Marion Bessin Liver
Research Center, Albert Einstein College of Medicine, Bronx, NY
10461
APStracts 2:0130G, 1995.
Since c-myc expression is increased during apoptosis in toxin-induced
liver injury in vivo, the role of c-myc in liver cell apoptosis was
investigated. The human hepatoma cell line HuH-7 which constitutively
expresses c-myc, was stably transfected with sense and anti-sense c
-myc expression vectors under the control of the zinc-inducible
metallothionein promoter. None of the three cell types (wild type,
sense c-myc, or anti-sense c-myc) underwent apoptosis when cultured
in serum-free medium (SFM). With the addition of SFM plus 37.5 [mu]M
zinc, wild type and sense c-myc expressing cells underwent rapid cell
death while anti-sense c-myc expressing cells exhibited increased
survival. This cell death had the light, fluorescent and electron
microscopic appearance of apoptosis, but did not result in DNA
fragmentation. This apoptosis could be terminated by the addition of
medium containing 2% fetal calf serum or the overexpression of bcl-2,
but not by supplementation with specific growth factors. Altering c
-myc expression did not affect cellular metallothionein mRNA levels,
or the rate of cell death from copper or cadmium. The requirement for
zinc and absence of DNA fragmentation in c-myc induced hepatoma cell
apoptosis under serum-free conditions provides further evidence of
the complex regulation of apoptosis in different cell types.
Received 21 November 1994; accepted in final form 16 June 1995.
APS Manuscript Number G456-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.