Overexpression of sigma-1 receptor in MCF-7 cells enhances proliferation via the classic protein kinase C subtype signaling pathway.

Abstract:

:Sigma-1 receptor (sigma-1R), a 25-kDa integral membrane protein, is expressed at a high density in various tumor cell lines and its ligands mediate tumor cell proliferation. However, the effect of this receptor on proliferation and the associated intracellular molecules in tumors remains unclear. The present study aimed to investigate the effect of sigma-1R overexpression on MCF-7 cell proliferation and the associated intracellular molecules that serve a key role in this process. The sigma-1R proliferative function was examined by comparing the proliferation rates of a sigma-1R-overexpressing line, MCF-41 with a sigma-1R-defective line, MCF-7, in culture media with various serum concentrations. The results demonstrated that MCF-41 cells grew significantly faster compared with MCF-7 cells, indicating a proliferation-enhancing receptor function. This proliferation-enhancing effect was completely eliminated by adding a PKC inhibitor to the culture media for MCF-41 cells. To identify which PKC subtype affects the proliferative function of sigma-1R, five inhibitors of PKC subtypes or enzymes involved in the PKC signaling cascade were introduced to MCF-7 and MCF-41 cell culture media and their effects on cell proliferation were compared. It was revealed that only the classic PKC subtype inhibitor, GF109203×, significantly inhibited MCF-41 cell proliferation compared with the MCF-7 line. In conclusion, among PKC iso-enzymes only classic PKC subtype enzymes serve an important role in sigma-1R overexpression enhancing MCF-7 cell proliferation.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Wu Y,Bai X,Li X,Zhu C,Wu ZP

doi

10.3892/ol.2018.9448

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

6763-6769

issue

5

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-9448

journal_volume

16

pub_type

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