Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 34
SDF1 controls pituitary cell proliferation through the activation of ERK1/2 and the
Ca2+-dependent cytosolic tyrosine kinase, Pyk2
°Alessandro Massa, *Silvia Casagrande, °Adriana Bajetto, °Carola Porcile, °Federica
Barbieri, °Stefano Thellung, °Sara Arena, °Alessandra Pattarozzi, °Monica Gatti,
°Alessandro Corsaro, *Mauro Robello, °Gennaro Schettini, °Tullio Florio.
°Section of Pharmacology, Dept. Oncology Biology and Genetics, University of Genova,
Italy. *Unit INFM, Dept. of Physics, University of Genova, Italy .
Stromal cell-Derived Factor 1 (SDF1) is a chemokine of the CXC subfamily involved in the
recruitment of immune cells to sites of inflammation. SDF1 exerts its effects interacting with
CXCR4, a G-protein coupled receptor. CXCR4 is often expressed by tumor cells and its
activation causes tumor cell proliferation. To date, no evidence have been provided on the
possible role of SDF1 in pituitary adenoma funcion, although it was reported the expression
of CXCR4 in rat pituitary. In this work, we used GH4C1 cells as a model to study the effects
of SDF1 in pituitary functions. In these cells, SDF1 induced dose-dependent proliferation.
Thus we evaluated the intracellular signaling involved in this effect. SDF1 increased cytosolic
[Ca2+] and activated Pyk2, ERK1/2 and BKCa channels. To correlate these intracellular
effectors with the proliferative activity we inhibited their activity using BAPTA-AM (Ca2+
chelator), PD98059 (MEK inhibitor), salicylate (Pyk2 inhibitor) and TEA (K+ channel
blocker). All these compounds reverted SDF1-induced proliferation, suggesting the
involvement of multiple intracellular pathways. To identify a possible cross-talk and a
molecular ordering among this pathways, we tested these antagonists on SDF1 dependent
activation of ERK1/2, Pyk2 and BKCa channels. We report that: the inhibition of [Ca2+]i
increase or BKCa channels activity did not affect ERK1/2 activation by SDF1; Pyk2
activation was purely Ca2+ dependent, not involving ERK1/2 or BKCa channels; BKCa
channels activity was antagonized by Pyk2 but not by ERK1/2 inhibitors. These data suggest
that SDF1- dependent increase of [Ca2+]i activates Pyk2, that, in turn, regulates BKCa
channel activity. Conversely, ERK1/2 activation is an independent phenomenon. In
conclusion we demonstrate that SDF1 causes proliferation of GH4C1 cells, suggesting that
the activation of CXCR4 may represent a novel regulatory mechanism for pituitary cell
proliferation, that may contribute to pituitary adenoma development.
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