title: Disorder, Promiscuous Interactions, and Stochasticity Regulate State Switching in the Unstable Prostate.
abstract: A causal link between benign prostatic hyperplasia (BPH) and prostate cancer has long been suspected but not widely accepted. A new model is proposed that supports such a connection. In contrast to the prevailing wisdom, our model, that draws on dynamical systems theory, suggests that in response to stress, epithelial cells in the unstable gland can give rise to both types of diseases via a phenotypic switching mechanism. The central idea is that phenotypic switching is a stochastic process which exploits the plasticity of the epithelial cell. It is driven by 'noise' contributed by the conformational dynamics of proteins that are intrinsically disordered. In a system that is noisy when stressed, disorder promotes promiscuity, unmasks latent information, and rewires the network to cause phenotypic switching. Cells with newly acquired phenotypes can transcend the traditional zonal boundaries to give rise to BPH or prostate cancer depending on the microenvironment. Establishing causality between the two diseases may provide us with an opportunity to better understand their etiology and guide prevention and treatment strategies. J. Cell. Biochem. 117: 2235-2240, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland.
authors.forename: Prakash
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: GTx Inc., Memphis, Tennessee.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Getzenberg
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013269:Stochastic Processes
keywords: BENIGN PROSTATIC HYPERPLASIA; CANCER/TESTIS ANTIGENS; PROSTATE CANCER; STATE SWITCHING