title: Intracellular kinetics of the androgen receptor shown by multimodal Image Correlation Spectroscopy (mICS).
abstract: 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.
authors.affiliation: Center for Applied Molecular Medicine, University of Southern, California, USA.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chiu
authors.affiliation: Center for Applied Molecular Medicine, University of Southern, California, USA.
authors.forename: Katherin
authors.initials: K
authors.lastname: Patsch
authors.affiliation: Translational Imaging Center, University of Southern, California, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cutrale
authors.affiliation: Center for Applied Molecular Medicine, University of Southern, California, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Soundararajan
authors.affiliation: Center for Applied Molecular Medicine, University of Southern, California, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Agus
authors.affiliation: Translational Imaging Center, University of Southern, California, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Fraser
authors.affiliation: Center for Applied Molecular Medicine, University of Southern, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ruderman
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D064847:Multimodal Imaging / Q000379:methods*; D021381:Protein Transport / Q000502:physiology; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen