ECE2014 Poster Presentations Endocrine tumours and neoplasia (99 abstracts)
The truncated somatostatin receptor sst5TMD4 stimulates the production of pro-angiogenic factors in in vitro and in vivo breast cancer models
Raul M Luque 1 , Mario Durán-Prado 1 , David Rincón-Fernández 1 , Marta Hergueta-Redondo 2 , Michael D Culler 3 , Gema Moreno-Bueno 2 , Manuel D Gahete 1 & Justo P Castaño 1
1Department of Cell Biology, Physiology and Immunology, University of Córdoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC) and CIBER Fisiopatología de la Obesidad y Nutrición, Cordoba, Spain; 2MD Anderson Cancer Center Madrid, Madrid, Spain; 3IPSEN, Milford, Massachusetts, USA.
The presence of the truncated somatostatin receptor sst5TMD4 has been correlated with poor prognosis in breast cancer tumorsand its overexpression in breast cancer derived cell lines is associated with increased cell malignancy. The objective of this study was to examine the cellular and molecular mechanisms underlying this association in order to identify new molecular targets for diagnosis, prognosis or therapy of these tumors. Accordingly, in this study, a breast cancer derived cell line (MCF7) stably transfected with the truncated receptor sst5TMD4 and its respective control (empty pCDNA3 plasmid) were used to perform a gene expressionarray to determine changes in the expression pattern induced by the presence of the sst5TMD4 receptor. This approach revealed the existence of a profound alteration in the expression of genes involved in several tumoral processes such as cell survival or angiogenesis. Interestingly, subsequent studies by qRT-PCR in the same cell lines showed that key components of the angiogenic process, including VEGF system, were also clearly overexpressed in sst5TMD4-overexpressed cells. These data were confirmed in a xenograft model of in vivo tumoral growth, where inoculation of MCF-7 cells transfected with sst5TMD4 induced higher levels of VEGF, at both RNA (qRT-PCR) and protein (western blot and immunocytochemistry), than xenografts inoculated with mock cells. Altogether, these data demonstrate that the presence of sst5TMD4 induces an overexpression of certain pro-angiogenic factors such as VEGF in the breast cancer cell line MCF7, and in a xenograft tumoral model derived from that cell line. Therefore, these results support the role of sst5TMD4 in tumor malignancy observed in breast cancer and may help in identifying new lines of actions for future drug therapies for these tumors.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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