Analogs of GnRH used for the treatment of sex steroid-independent tumors are not optimal because of endocrine side-effects. Lamprey gonadotropin-releasing hormone III (lGnRH-III), however, directly inhibits the growth of several tumor cell lines derived from reproductive organs. In this study, the signaling and antiproliferative effects of lGnRH-III on two breast, a colonic and a pancreatic cancer cell lines were investigated. Binding affinity of the peptide was determined by competitive receptor binding assays. Cell proliferation was measured following treatment for 3 days with lGnRH-III. Intracellular cAMP levels in response to lGnRH-III binding were quantified and effects of pertussis toxin (PTX), an inhibitor of Gi activation, on suppression of growth by lGnRH-III were examined. lGnRH-III had comparable affinities for receptors on all four cell lines and inhibited their growth at micromolar concentrations in a dose-dependent manner. PTX-sensitive decrease in cAMP levels in response to lGnRH-III in colonic and pancreatic cells was observed, while lGnRH-III increased intracellular [Ca2+] in both breast cancer cell lines. This study further indicates that the same receptors utilize different signal transduction pathways in different cancer cells.
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Acknowledgments
This work was supported by NIH Grant Number 1 P20 RR16469 from the BRIN program of the National Center of Research Resources and Carpenter Chair in Biochemistry, Creighton University, Omaha, NE. The authors would like to thank Dr. Ward Pedersen for kindly providing the instruments for the cAMP and intracellular [Ca2+] measurements and Dr. John A. Yee for helpful discussion.
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Herédi-Szabó, K., Murphy, R.F. & Lovas, S. Different Signal Responses to Lamprey GnRH-III in Human Cancer Cells. Int J Pept Res Ther 12, 359–364 (2006). https://doi.org/10.1007/s10989-006-9039-y
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DOI: https://doi.org/10.1007/s10989-006-9039-y