Subcellular localization of sigma-2 receptors in breast cancer cells using two-photon and confocal microscopy.
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| 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 approximately 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.
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| Authors | 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 |
| Journal | Cancer research (Cancer Res) Vol. 67 Issue 14 Pg. 6708-16 (Jul 15 2007) ISSN: 0008-5472 [Print] United States |
| PMID | 17638881 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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