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The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells

Oncogene volume 31, pages 2049–2061 (2012)Cite this article

Abstract

Somatostatin receptors (sst1–5) are present in different types of tumors, where they inhibit key cellular processes such as proliferation and invasion. Although ssts are densely expressed in breast cancer, especially sst2, their role and therapeutic potential remain uncertain. Recently, we identified a new truncated sst5 variant, sst5TMD4, which is related to the abnormal response of certain pituitary tumors to treatment with somatostatin analogs. Here, we investigated the possible role of sst5TMD4 in breast cancer. This study revealed that sst5TMD4 is absent in normal mammary gland, but is abundant in a subset of poorly differentiated human breast tumors, where its expression correlated to that of sst2. Moreover, in the MCF-7 breast cancer model cell, sst5TMD4 expression increased malignancy features such as invasion and proliferation abilities (both in cell cultures and nude mice). This was likely mediated by sst5TMD4-induced increase in phosphorylated extracellular signal-regulated kinases 1 and 2 and p-Akt levels, and cyclin D3 and Arp2/3 complex expression, which also led to mesenchymal-like phenotype. Interestingly, sst5TMD4 interacts physically with sst2 and thereby alters its signaling, enabling disruption of sst2 inhibitory feedback and providing a plausible basis for our findings. These results suggest that sst5TMD4 could be involved in the pathophysiology of certain types of breast tumors.

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Acknowledgements

This work was supported by BIO-0139, CTS-01705, CTS-5051, BFU2004-03883, BFU2007-60180/BFI, BFU2008-01136-BFI, BFU2010-19300, FPU-AP20052473, FI06-00804, SAF2007-63075, SAF2007-63075/FMM07, SAF2010-201075, CD07/00246, RYC-2007-00186 and IPSEN. Ciber is an initiative of the Instituto de Salud Carlos III.

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Author notes

  1. M Durán-Prado and M D Gahete: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, Physiology and Immunology, University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain

    M Durán-Prado, M D Gahete, A J Martínez-Fuentes, J Córdoba-Chacón, F Gracia-Navarro, M M Malagón, R M Luque & J P Castaño

  2. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas ‘Alberto Sols’, CSIC-UAM, IdiPAZ (Instituto de Investigación Sanitaria La Paz), Madrid, Spain

    M Hergueta-Redondo & G Moreno-Bueno

  3. Fundación MD Anderson Internacional, Madrid, Spain

    M Hergueta-Redondo & G Moreno-Bueno

  4. Servicio de Anatomía Patológica, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain

    J Palacios

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Correspondence to J P Castaño.

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Competing interests

JPC receives research funds from Ipsen and Novartis. MDP, AJMF, FGN, MMM and JPC are listed as inventors of patent PCT/ES2007/00627 for the commercial use of sst5TMD4. The remaining authors declare no conflict of interest.

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Durán-Prado, M., Gahete, M., Hergueta-Redondo, M. et al. The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells. Oncogene 31, 2049–2061 (2012). https://doi.org/10.1038/onc.2011.389

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