The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells

Investor logo

Warning

This publication doesn't include Faculty of Economics and Administration. It includes Faculty of Medicine. Official publication website can be found on muni.cz.
Authors

PERNICOVÁ Zuzana SLABÁKOVÁ Eva FEDR Radek ŠIMEČKOVÁ Šárka JAROŠ Josef SUCHÁNKOVÁ Tereza BOUCHAL Jan KHARAISHVILI Gvantsa KRÁL Milan KOZUBÍK Alois SOUČEK Karel

Year of publication 2014
Type Article in Periodical
Magazine / Source Molecular Cancer
MU Faculty or unit

Faculty of Medicine

Citation
Web https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-113
Doi http://dx.doi.org/10.1186/1476-4598-13-113
Field Genetics and molecular biology
Keywords Androgen depletion; cAMP signaling; Cell cycle arrest; High cell density; Neuroendocrine transdifferentiation
Description Background: Tumor heterogeneity and the plasticity of cancer cells present challenges for effective clinical diagnosis and therapy. Such challenges are epitomized by neuroendocrine transdifferentiation (NED) and the emergence of neuroendocrine-like cancer cells in prostate tumors. This phenomenon frequently arises from androgen-depleted prostate adenocarcinoma and is associated with the development of castration-resistant prostate cancer and poor prognosis.Results: In this study, we showed that NED was evoked in both androgen receptor (AR)-positive and AR-negative prostate epithelial cell lines by growing the cells to a high density. Androgen depletion and high-density cultivation were both associated with cell cycle arrest and deregulated expression of several cell cycle regulators, such as p27Kip1, members of the cyclin D protein family, and Cdk2. Dual inhibition of Cdk1 and Cdk2 using pharmacological inhibitor or RNAi led to modulation of the cell cycle and promotion of NED. We further demonstrated that the cyclic adenosine 3, 5-monophosphate (cAMP)-mediated pathway is activated in the high-density conditions. Importantly, inhibition of cAMP signaling using a specific inhibitor of adenylate cyclase, MDL-12330A, abolished the promotion of NED by high cell density.Conclusions: Taken together, our results imply a new relationship between cell cycle attenuation and promotion of NED and suggest high cell density as a trigger for cAMP signaling that can mediate reversible NED in prostate cancer cells.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.