Subcellular localization of sigma-2 receptors in breast cancer cells using two-photon and confocal microscopy

Chenbo Zeng, Suwanna Vangveravong, Jinbin Xu, Katherine C. Chang, Richard S. Hotchkiss, Kenneth T. Wheeler, Duanwen Shen, Zhi Ping Zhuang, Hank F. Kung, Robert H. Mach

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Sigma-2 receptor agonists have been shown to induce cell death via caspase-dependent and caspase-independent pathways. Unfortunately, there is little information regarding the molecular function of sigma-2 receptors that can explain these results. In this study, two fluorescent probes, SW107 and K05-138, were used to study the subcellular localization of sigma-2 receptors by two-photon and confocal microscopy. The results indicate that sigma-2 receptors colocalize with fluorescent markers of mitochondria, lysosomes, endoplasmic reticulum, and the plasma membrane in both EMT-6 mouse and MDA-MB-435 human breast cancer cells. The fluorescent probe, K05-138, was internalized rapidly, reaching a plateau of fluorescent intensity at 5 min. The internalization of K05-138 was reduced ∼40% by phenylarsine oxide, an inhibitor of endocytosis. These data suggest that sigma-2 ligands are internalized, in part, by an endocytotic pathway. The localization of sigma-2 receptors in several organelles known to have a role in both caspase-dependent and caspase-independent pathways of cell death supports the conclusions of previous studies suggesting that sigma-2 receptor ligands should be evaluated as potential cancer chemotherapeutic agents.

Original languageEnglish
Pages (from-to)6708-6716
Number of pages9
JournalCancer research
Volume67
Issue number14
DOIs
StatePublished - Jul 15 2007

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