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Characterization and sub-cellular localization of SS1R, SS2R, and SS5R in human late-stage prostate cancer cells: effect of mono- and bi-specific somatostatin analogs on cell growth.

Abstract：

:Somatostatin (SST) and SST receptors (SS1R, SS2R, SS3R, SS4R and SS5R) appear to play a significant role in the progression of human prostate cancer (PCa), which is associated with heterogeneity of SSRs expression and specific cell localization as we already demonstrated in the LNCaP cell line, an in vitro model of human androgen-dependent PCa. In this study, PC-3 and DU-145 human castration-resistant PCa cells were found to express all SSRs, while LNCaP expressed all but SS4R. A 48-h treatment with BIM-23244 (SS2R/SS5R) or BIM-23926 (SS1R) SST analogs was more effective in inhibiting cell proliferation, compared to BIM-23120 (SS2R), BIM-23206 (SS5R) and BIM-23704 (SS1R/SS2R). BIM-23926 (SS1R) treatment increased the amount of p21 and decreased phosphorylated (p) ERK1/2. BIM-23244 (SS2R/SS5R) led to p21 increment only in PC-3 cells, and to pERK1/2 reduction in both cell lines. SS1R/SS2R and SS2R/SS5R receptor dimers were natively present on cell membrane and their amount was increased by BIM-23704 (SS1R/SS2R) or BIM-23244 (SS2R/SS5R) treatment, respectively. SS1R, SS2R and SS5R were differently distributed among nuclear, lysosomal and microsomal compartment, according to their different recycling dynamics. These results show that, in PC-3, DU-145 and LNCaP cells, activation of SS1R and SS2R/SS5R leads to relevant antiproliferative effects.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Ruscica M,Magni P,Steffani L,Gatto F,Albertelli M,Rametta R,Valenti L,Ameri P,Magnaghi V,Culler MD,Minuto F,Ferone D,Arvigo M

doi

10.1016/j.mce.2013.10.027

subject

Has Abstract

pub_date

2014-02-15 00:00:00

pages

860-70

issue

2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(13)00467-X

journal_volume

382

pub_type

杂志文章

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