Cell Growth & Differentiation, Vol 7, Issue 5 563-572, Copyright © 1996 by American Association of Cancer Research
Nonconstitutive expression of the gastrin-releasing peptide autocrine growth system in human small cell lung carcinoma NCI-H345 cells
SM Aguayo, Y Miller, D Boose, M Holley, LB Portanova, KD Schuyler and MA Kane
Department of Medicine, Atlanta Veterans Affairs Medical Center, Georgia 30033, USA.
Constitutive, unregulated autocrine growth is thought to be an important
mechanism whereby cancer cells gain a proliferative advantage over
nonmalignant cells. The question addressed here was whether the autocrine
growth system for gastrin-releasing peptide (GRP) in human small cell lung
carcinoma cells is, in fact, always expressed in a constitutive,
unregulated fashion. Lag, rapid, and plateau growth states were defined for
small cell lung carcinoma NCI-H345 cells based on periods during which they
expressed different growth rates after plating as single cell suspensions.
Immunoreactive GRP in the conditioned medium and in NCI-H345 cells
harvested during each of these growth states, as well as cell DNA content,
GRP mRNA expression, specific 125I-GRP uptake, specific 125I-GRP binding to
solubilized membranes, and GRP and neuromedin B receptor mRNA expression by
reverse transcription-PCR were analyzed. Maximal levels of GRP expression
were observed during the lag growth state, with the highest concentration
of immunoreactive GRP in the conditioned medium during the rapid growth
state. Specific 125I-GRP uptake and binding were also highest during the
lag growth state; however, GRP receptor mRNA did not significantly change.
In contrast to prevailing concepts, these studies support the conclusion
that the expression of the GRP autocrine growth system in NCI-H345 cells is
indeed regulated. Furthermore, the components are maximally expressed
before rapid growth begins, suggesting that other mechanisms are activated
to support the actual proliferation.