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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 a 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, roč.~13, č.~1, s.~1-16. ISSN~1476-4598. Dostupné z: https://dx.doi.org/10.1186/1476-4598-13-113.
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