Disorder, Promiscuous Interactions, and Stochasticity Regulate State Switching in the Unstable Prostate. Issue 10 (3rd June 2016)

• Record Type: Journal Article
• Authors: Kulkarni, Prakash; Getzenberg, Robert H.
• Is Part Of: Journal of cellular biochemistry. Volume 117:Issue 10(2016:Oct.)
• Page Start: 2235
• Page End: 2240
• Publication Date: 2016-06-03
• Subjects: PROSTATE CANCER -- BENIGN PROSTATIC HYPERPLASIA -- CANCER/TESTIS ANTIGENS -- STATE SWITCHING; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25578
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : A causal link between benign prostatic hyperplasia (BPH) and prostate cancer has long been suspected but not widely accepted. A new integrated model describing the origins of both diseases is proposed that supports such a connection.