Latest Publications

@article{pernicova_role_2014,

title = {The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells.},

author = {Zuzana Pernicová and Eva Slabáková and Radek Fedr and Šárka Šimečková and Josef Jaroš and Tereza Suchánková and Jan Bouchal and Gvantsa Kharaishvili and Milan Král and Alois Kozubík and Karel Souček},

doi = {10.1186/1476-4598-13-113},

issn = {1476-4598},

year  = {2014},

date = {2014-05-01},

journal = {Molecular cancer},

volume = {13},

pages = {113},

abstract = {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.},

note = {Place: England},

keywords = {*Cell Transdifferentiation/drug effects, Androgen/metabolism, Androgens/pharmacology, CDC2 Protein Kinase, Cell Count, Cell Cycle Checkpoints/drug effects, Cell Line, Cyclic AMP/metabolism, Cyclin-Dependent Kinase 2/metabolism, Cyclin-Dependent Kinases/metabolism, Epithelial Cells/drug effects/enzymology/pathology, Humans, Immunohistochemistry, Male, Neuroendocrine Cells/drug effects/*pathology, Prostatic Neoplasms/*pathology, Protein Kinase Inhibitors/pharmacology, Receptors, Signal Transduction/drug effects, Tumor},

pubstate = {published},

tppubtype = {article}

}

@article{vondracek_induction_2004,

title = {Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans.},

author = {Jan Vondrácek and Katerina Chramostová and Martina Plísková and Ludek Bláha and Werner Brack and Alois Kozubík and Miroslav Machala},

doi = {10.1897/03-620},

issn = {0730-7268},

year  = {2004},

date = {2004-09-01},

journal = {Environmental toxicology and chemistry},

volume = {23},

number = {9},

pages = {2214–2220},

abstract = {A group of heterocyclic aromatic compounds, dinaphthofurans (DNFs), recently have been identified as potentially significant contaminants in freshwater sediments. In the present study, a battery of in vitro assays was used for detection of toxic effects of DNFs that are potentially associated with endocrine disruption and tumor promotion. Dinaphthofurans were found to act as relatively potent inducers of aryl hydrocarbon receptor (AhR)-mediated activity in the chemical-activated luciferase reporter gene expression DR-CALUX assay. The relative AhR-inducing potencies of DNFs were similar or even higher than relative potencies of unsubstituted polycyclic aromatic hydrocarbons (PAHs), with dinaphtho[1,2-b;2'3'-d]furan being the most potent AhR agonist. Two compounds, dinaphtho[2,1-b;2'3'-d]furan and dinaphtho[1,2-b;1'2'-d]furan, induced estrogen receptor (ER)-mediated activity in the estrogen receptor-mediated CALUX (the ER-CALUX) assay. Two types of potential tumor-promoting effects of DNFs were investigated, using in vitro bioassays for detection of inhibition of gap-junctional intercellular communication and detection of a release from contact inhibition. Although the acute inhibition of gap-junctional intercellular communication was not observed, all six tested DNFs were able to release rat liver epithelial WB-F344 cells from contact inhibition at concentrations as low as 100 nM. In summary, the present study indicated that DNFs can exert multiple biological effects in vitro, including induction of the AhR-mediated activity, release of cells from contact inhibition, and induction of ER-mediated activity.},

note = {Place: United States},

keywords = {Animals, Aryl Hydrocarbon/*drug effects, Carcinogens, Cell Count, Cell Line, Cell Proliferation/drug effects, Environmental/*pharmacology, Estrogen/*drug effects, Estrogens/*pharmacology, Furans/*pharmacology, Molecular Structure, Naphthalenes/*pharmacology, Rats, Receptors, S Phase/drug effects, Tumor},

pubstate = {published},

tppubtype = {article}

}

@article{hoferova_tumor-host_2003,

title = {Tumor-host interactions accompanying the growth of the G:5:113 fibrosarcoma in the mouse: possibilities for a new therapeutic approach?},

author = {Zuzana Hoferová and Antonín Vacek and Michal Hofer and Nadezda O. Macková and Karel Soucek and Alena Egyed and Peter Fedorocko},

doi = {10.1081/cnv-120016419},

issn = {0735-7907},

year  = {2003},

date = {2003-04-01},

journal = {Cancer investigation},

volume = {21},

number = {2},

pages = {227–236},

abstract = {The experiments were aimed at describing in detail some interactions between a solid tumor growing from subcutaneously transplanted G:5:113 fibrosarcoma cells in vivo and its mouse host. The tumor was found to elevate significantly the number of granulocytes in the peripheral blood of the host after having achieved the volume of about 1 cm3 (day 40 after transplantation). Blood plasma from fibrosarcoma-bearing mice stimulated proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in vitro and suppressed growth of G:5:113 cell population in culture. Interestingly, both effects were observable as early as week 1 when the tumor was still macroscopically invisible and unpalpable. Conditioned medium from cultures of G:5:113 fibrosarcoma cells stimulated proliferation of GM-CFC in vitro. These findings might represent a starting point for studies aimed at designing new therapeutic approaches for the treatment of fibrosarcoma.},

note = {Place: England},

keywords = {Animals, Cell Count, Cell Cycle/*physiology, Cell Division, Cell Survival/*physiology, Conditioned, Culture Media, Cultured, Fibrosarcoma/blood/*pathology, Granulocytes/pathology, Inbred C3H, Leukocyte Count, Mice, Tumor Cells},

pubstate = {published},

tppubtype = {article}

}