TY - JOUR
T1 - Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation
AU - Ferone, Diego
AU - Arvigo, Marica
AU - Semino, Claudia
AU - Jaquet, Philippe
AU - Saveanu, Alexandru
AU - Taylor, John E.
AU - Moreau, Jacques Pierre
AU - Culler, Michael D.
AU - Albertelli, Manuela
AU - Minuto, Francesco
AU - Barreca, Antonina
PY - 2005/12
Y1 - 2005/12
N2 - To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst 2 and D 2R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst 2 and the long isoform of the D 2R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst 5 and to a lesser extent sst 3 and D 4R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [ 3H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P <0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.
AB - To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst 2 and D 2R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst 2 and the long isoform of the D 2R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst 5 and to a lesser extent sst 3 and D 4R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [ 3H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P <0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.
KW - Dopamine receptors
KW - Growth factors
KW - Lung carcinoma
KW - Receptor dimerization
KW - Somatostatin receptors
UR - http://www.scopus.com/inward/record.url?scp=33644664300&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33644664300&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00209.2005
DO - 10.1152/ajpendo.00209.2005
M3 - Article
C2 - 16046458
AN - SCOPUS:33644664300
VL - 289
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 6
ER -