The antiproliferative effects of somatostatin receptor subtype 2 in breast cancer cells.
OBJECTIVE
Somatostatin receptor subtype 2 (SSTR2) is the principal mediator of somatostatin's (SST) antiproliferative effects on normal and cancer cells. Therefore, we investigated whether the enhanced expression of SSTR2 could inhibit the proliferation of tumor cells, and, if so, the mechanisms that might be involved.


METHODS
SSTR2 expression levels were determined by qRT-PCR in several tumor cell lines. Then, a plasmid pIRES2-EGFP-SSTR2 (pSIG) was constructed and stably transfected into MCF-7 cells (MCF-7/pSIG). After SSTR2 overexpression was identified by qRT-PCR, immunofluorescence staining and a receptor binding assay, the MCF-7/pSIG cells were analyzed by PI staining for apoptosis and cell cycle arrest was tested by flow cytometry for epidermal growth factor receptor (EGFR) expression. The EGF-stimulated proliferation of MCF-7 cells was assayed by MTT.


RESULTS
The human breast cancer cell line MCF-7 expresses a lower level of SSTR2, thereby partly accounting for the decreased response to SST. The overexpression of SSTR2 in MCF-7 cells resulted in apoptosis, cytostasis and G(1)/S cell cycle arrest. Furthermore, the expression of EGFR, together with EGF-stimulated proliferation, was markedly decreased in the MCF-7/pSIG cells.


CONCLUSIONS
Enhanced SSTR2 expression played an antiproliferative role in MCF-7 cells through inducing apoptosis and G(1)/S cell cycle arrest, and also by decreasing EGFR expression, thereby counteracting the growth-stimulating effect of EGF. Our data seem to indicate that developing a new therapeutic agent capable of upregulating SSTR expression could potentially be a way to block tumor progression.Acta Pharmacologica Sinica (2009) 30: 1053-1059; doi: 10.1038/aps.2009.59.
He
Yong
Y
Department of Nuclear Medicine, Hubei Key Laboratory of Molecular Imaging, Union hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Yuan
Xiao-Mei
XM
Lei
Ping
P
Wu
Sha
S
Xing
Wei
W
Lan
Xiao-Li
XL
Zhu
Hui-Fen
HF
Huang
Tao
T
Wang
Guo-Bing
GB
An
Rui
R
Zhang
Yong-Xue
YX
Shen
Guan-Xin
GX
D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D066246:ErbB Receptors