PNNL-13501 - Pacific Northwest National Laboratory

Anchorage-Independent Growth
(% control)
160
140
120
100
0.1 ng/ml EGF
10 nM 8-iso-PGF2α
+
-
Figure 3. 8-iso-PGF 2α increases anchorage-independent, but
-dependent growth of the MCF-7 human breast cancer cell
line
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+
+
+
Figure 4. Modulation of human renal epithelial
proliferation (HK-2) by prototypical isoprostanes
8-iso-PGE2 and 8-iso-PGF2α increased proliferation in a
concentration-dependent fashion (Figure 4). Importantly,
the proliferative response was apparent at pM-nM
concentrations.
Summary and Conclusions
Prototypical isoprostanes modulate anchorage-dependent
and anchorage-independent growth of several in vitro
model systems derived from experimental animal models
(JB6, rat aortic SMCs, B6C3F1 mouse) and of human
origin (HK-2, MCF-7). Importantly, the cellular response
to prototypical isoprostanes was apparent at extremely
low concentration (pM-nM) in all model systems,
suggesting the biological activity of the isoprostanes is
physiologically relevant. We looked to correlate
isoprostane responsiveness with known prostanoid
receptor pharmacology, however, we found no clear
correlation. Further complicating the interpretation of our
results was the differential responsiveness of model
systems to isoprostanes under anchorage-dependent and
-independent conditions, as well as potential differences
in signal transduction crosstalk with epidermal growth
factor-dependent signaling. Therefore, the role of
isoprostanes in physiology and pathophysiology must be
determined in a cell type and organ specific fashion.
Presentation
A seminar entitled “Cellular transformation by
prostanoids and isoprostanes: linking response to
G-protein coupled receptors” was presented at the
National Institutes of Health, National Cancer Institute,
Frederick, Maryland, November 1999.
Biosciences and Biotechnology 83