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@article{1225576,
author = {Pernicová, Zuzana and Slabáková, Eva and Fedr, Radek and Šimečková, Šárka and Jaroš, Josef and Suchánková, Tereza and Bouchal, Jan and Kharaishvili, Gvantsa and Král, Milan and Kozubík, Alois and Souček, Karel},
article_location = {London},
article_number = {1},
doi = {http://dx.doi.org/10.1186/1476-4598-13-113},
keywords = {Androgen depletion; cAMP signaling; Cell cycle arrest; High cell density; Neuroendocrine transdifferentiation},
language = {eng},
issn = {1476-4598},
journal = {Molecular Cancer},
title = {The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells},
url = {https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-113},
volume = {13},
year = {2014}
}
TY - JOUR
ID - 1225576
AU - Pernicová, Zuzana - Slabáková, Eva - Fedr, Radek - Šimečková, Šárka - Jaroš, Josef - Suchánková, Tereza - Bouchal, Jan - Kharaishvili, Gvantsa - Král, Milan - Kozubík, Alois - Souček, Karel
PY - 2014
TI - The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells
JF - Molecular Cancer
VL - 13
IS - 1
SP - 1-16
EP - 1-16
PB - BioMed Central
SN - 14764598
KW - Androgen depletion
KW - cAMP signaling
KW - Cell cycle arrest
KW - High cell density
KW - Neuroendocrine transdifferentiation
UR - https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-113
L2 - https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-113
N2 - 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.
ER -
PERNICOVÁ, Zuzana, Eva SLABÁKOVÁ, Radek FEDR, Šárka ŠIMEČKOVÁ, Josef JAROŠ, Tereza SUCHÁNKOVÁ, Jan BOUCHAL, Gvantsa KHARAISHVILI, Milan KRÁL, Alois KOZUBÍK and Karel SOUČEK. The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells. \textit{Molecular Cancer}. London: BioMed Central, 2014, vol.~13, No~1, p.~1-16. ISSN~1476-4598. Available from: https://dx.doi.org/10.1186/1476-4598-13-113.
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