Expression and selective activation of somatostatin receptor subtypes induces cell cycle arrest in cancer cells

Zou,Yi; Tan,Haiping; Zhao,Yuanfeng; Zhou,Yuan; Cao,Lin

doi:10.3892/ol.2018.9773

Expression and selective activation of somatostatin receptor subtypes induces cell cycle arrest in cancer cells

Authors:
- Yi Zou
- Haiping Tan
- Yuanfeng Zhao
- Yuan Zhou
- Lin Cao
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Affiliations: Department of Biology, School of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Anesthesiology of Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China
Published online on: November 28, 2018 https://doi.org/10.3892/ol.2018.9773
Pages: 1723-1731
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Somatostatin receptors (SSTRs) are G‑protein‑coupled plasma membrane receptors that have been determined to be expressed in normal and cancer tissues. Activation of SSTRs frequently results in inhibition of cell proliferation and therefore somatostatin analogues (SSAs) have been used in cancer treatment. However, the variable outcomes of SSA treatment were considered to be the consequences of loss‑of‑expression of SSTRs and/or subtype‑specific effects. In the present study, the patterns of SSTR expression in 160 breast cancer tissues were investigated, and the mechanisms of SSTR activation and the influence on cell proliferation were further characterized. The expression levels of SSTR1‑5 were determined using immunohistology. Hemagglutinin‑SSTR1 and MYC‑SSTR4 were transiently overexpressed in MDA‑MB‑435S cells, and the potential receptor dimerization was determined using immunofluorescence and co‑immunoprecipitation. The influence of SSTR1 and SSTR4 expression/activation on cell proliferation was monitored using flow cytometry. The results demonstrated that all five SSTR subtypes were expressed at variable levels in tumor tissues, with the highest positive expression instance being determined for SSTR1 and SSTR4, with positive expression levels in 90.0 and 71.3% of tumor tissues, respectively. Immunofluorescence and co‑immunoprecipitation revealed SSTR1/SSTR4 heterodimerization, which was increased in response to receptor activation using the subtype‑specific SSA L‑803087. The translocation of SSTR1/SSTR4 dimers into the cytoplasm upon receptor activation was also observed. Additionally, it was identified using flow cytometry that co‑expression and activation of SSTR1 and SSTR4 in MDA‑MB‑435S cells resulted in a decreased proportion of S‑phase cells. The results of the present study revealed that SSTR1 and SSTR4 are the most frequently expressed SSTR subtypes in breast cancer, and that the cell cycle arrest was mediated by SSTR1/SSTR4 dimerization/activation.

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