Activation of nuclear estrogen receptors induced by low-power laser irradiation via PI3-K/Akt signaling cascade.
Low-power laser irradiation (LPLI) has been shown to exert promotive effects on cell survival and proliferation through activation of various signaling pathways. Estrogen receptors (ERs, ERα, and ERβ) are ligand-activated transcription factors, which regulate target gene expression, promote cell proliferation, and resist apoptosis. However, it is unclear whether LPLI could induce ligand-independent activation of ERs. In the present study, we investigated the subcellular pools, nuclear redistribution, and transcriptional activity of ERs under LPLI (1.2 J/cm(2), 633 nm) treatment using single-molecule fluorescence imaging and dual-luciferase reporter assay. We found that ERs were not only localized to nucleus, but also existed in mitochondria. Moreover, we found that LPLI induced nuclear redistribution and transcriptional activity of ERs in a ligand-independent manner. Our further investigation showed that PI3-K/Akt signaling cascade was involved in LPLI-induced activation of ERs. Wortmannin, a PI3-K inhibitor, or triciribine (API-2), a specific Akt inhibitor, potently suppressed the nuclear redistribution and transcriptional activity of ERs induced by LPLI, revealing that PI3-K/Akt signaling cascade was required for the activation of ERs induced by LPLI. Collectively, we demonstrated the first time that LPLI induced the ligand-independent nuclear redistribution and transcriptional activity of ERs, which were dependent on the activity of PI3-K/Akt. Our findings provide direct evidence for the molecular mechanisms of LPLI-induced transcription factor activation.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
Lei
L
Huang
Yonghong
Y
Tang
Da
D
Xing
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D002522:Chlorocebus aethiops; D004967:Estrogens / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D056945:Hep G2 Cells; D006801:Humans; D028022:Low-Level Light Therapy; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000528:radiation effects; D000077191:Wortmannin
D000730:Androstadienes; D004967:Estrogens; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D012263:Ribonucleosides; D000077191:Wortmannin; C023764:triciribine