Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS)
| Autor: | David B. Agus, Scott E. Fraser, Francesco Cutrale, Chi-Li Chiu, Daniel Ruderman, Katherin Patsch, Anjana Soundararajan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytoplasm Fluorescence-lifetime imaging microscopy Cell Multimodal Imaging Article 03 medical and health sciences 0302 clinical medicine Microtubule medicine Humans Nuclear membrane Cell Nucleus Multidisciplinary Chemistry 3. Good health Androgen receptor Protein Transport 030104 developmental biology medicine.anatomical_structure Receptors Androgen 030220 oncology & carcinogenesis Biophysics Nucleus Intracellular HeLa Cells |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep22435 |
| Popis: | The androgen receptor (AR) pathway plays a central role in prostate cancer (PCa) growth and progression and is a validated therapeutic target. In response to ligand binding AR translocates to the nucleus, though the molecular mechanism is not well understood. We therefore developed multimodal Image Correlation Spectroscopy (mICS) to measure anisotropic molecular motion across a live cell. We applied mICS to AR translocation dynamics to reveal its multimodal motion. By integrating fluorescence imaging methods we observed evidence for diffusion, confined movement and binding of AR within both the cytoplasm and nucleus of PCa cells. Our findings suggest that in presence of cytoplasmic diffusion, the probability of AR crossing the nuclear membrane is an important factor in determining the AR distribution between cytoplasm and the nucleus, independent of functional microtubule transport. These findings may have implications for the future design of novel therapeutics targeting the AR pathway in PCa. |
| Databáze: | OpenAIRE |
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