Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 4
Mallory Body Keratin Aggresomes Form in Response to Integrin Initiated Cell
Signaling MAP Kinase pathway
Fawzia Bardag-Gorce, Yong Wu, Latoiya Wilson, Jun Li, Li Nan, Barbara A. French
and Samuel W. French.
LABioMed at Harbor UCLA Medical Center. Torrance, CA, 90502. USA.
Mallory body formation is observed in the liver cells of alcoholic patients, as well as in other
non-alcoholic diseases. Several factors, including proteasome inhibition, are hypothesized to
be the cause of this phenomenon of MB formation. Feeding mice the drug diethyl-1, 4dihydro-2,
4, 6-trimethyl-3, 5-pyridinedicarboxylate (DDC) for 10 weeks, is a good model to
study Mallory body formation. Recent study showed that the primary culture of hepatocytes
isolated from the liver of these drug primed mice is also a good in vitro model to study this
phenomenon.
The MB formation was in several case associated with tumor formation. In these drugprimed
mice tumor growth was noticed in the liver of mice where the tumor cells showed also
formation of MB. The mitogen–activated protein kinase pathway, a central regulator of
tumor growth and cell differentiation, was studied to further examine the array of factors
leading to Mallory body formation. MEK is a central focus of the pathway and it is
associated with the up regulation by phosphorylating of the map kinase P44/42 (ERK &).
Western blot analysis exhibited increased phosphorylation of p44/42, which was associated
with an increase of Mallory body formation in liver cells of mice fed DDC. In the DDCprimed
primary culture of hepatocytes there was a marked MBs formation and this formation
was significantly reduced when U0126, an inhibitor of MEK1 protein, which reduced
significantly the phosphorylated forms of ERK1/2. Other tumor markers such as AFP, was
examined and showed an increase in the protein level when the mice were fed DDC and
where a significant amount of MBs were formed. This data are consistent with the conclusion
that Mallory body formation is associated with preneoplastic state of the cell.
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