Visit our Expo - Redox and Inflammation signaling 2012

Session III : Protein kinase cascades as therapeutic targets Poster III, 7
Proliferation of human melanoma cells related to high expression of PKA regulatory
subunit 1A protein
Sara Bondioni, Erika Peverelli , Monica Rodolfo1 ,Stefano Ferrero 2, Silvano Bosari 2,
Paolo Beck-Peccoz Anna Spada, Andrea Lania and Giovanna Mantovani.
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS,
1Istituto Nazionale dei Tumori and 2Pathology Unit, Department of Medicine, Surgery
and Dentistry, A.O. San Paolo and Ospedale Maggiore IRCCS; Milan, Italy.
The two regulatory subunits (R1 and R2) of PKA are differentially expressed in several
cancer cell lines and studies indicate distinct roles for these subunits in growth control. The
aim of this study was to evaluate the expression of the different PKA regulatory subunits
(R1A, R2A, R2B) in human melanomas, as well as the effects of selective subunit activation
on cell proliferation. Immunohystochemistry demonstrated high expression levels of the three
PKA regulatory subunits studied in all melanoma samples. On the contrary, in normal
melanocytes R1A was absent or expressed at very low levels, suggesting a higher R1/R2 ratio
in tumoral tissue compared to normal one. The effect of R1/R2 ratio on proliferation was
assessed in 6 human melanoma cell lines that show the same PKA regulatory subunits
expression pattern of melanoma samples. The R2-selective cAMP analogue 8-Cl-cAMP dosedependently
inhibited cell proliferation (60% inhibition at 5 M 8-Cl-cAMP) through the
induction of apoptosis. Inhibition of cell proliferation was also obtained by R1A silencing
through siRNA technique. Our data indicate that a high R1/R2 ratio promotes proliferation in
human melanoma cells.
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