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

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

Oncol Lett. 2019 Feb;17(2):1723-1731

Authors: Zou Y, Tan H, Zhao Y, Zhou Y, Cao L

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.

PMID: 30675231 [PubMed]

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