Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornelio,Daniela  B.; De Farias,Caroline  B.; Prusch,Débora  S.; Heinen,Tiago  E.; Dos Santos,Rafael  P.; Abujamra,Ana  L.; Schwartsmann,Gilberto; Roesler,Rafael

doi:10.3892/mco.2012.7

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Authors:
- Daniela B. Cornelio
- Caroline B. De Farias
- Débora S. Prusch
- Tiago E. Heinen
- Rafael P. Dos Santos
- Ana L. Abujamra
- Gilberto Schwartsmann
- Rafael Roesler
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Affiliations: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil, Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil, National Institute for Translational Medicine (INCT-TM), Porto Alegre, RS, Brazil, Children's Cancer Institute, Porto Alegre, RS, Brazil, Department of Internal Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
Published online on: August 7, 2012 https://doi.org/10.3892/mco.2012.7
Pages: 148-152

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Abstract

Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription‑polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.

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