Latest Publications

@article{slabakova_alternative_2017,

title = {Alternative mechanisms of miR-34a regulation in cancer.},

author = {Eva Slabáková and Zoran Culig and Ján Remšík and Karel Souček},

doi = {10.1038/cddis.2017.495},

issn = {2041-4889},

year  = {2017},

date = {2017-10-01},

journal = {Cell death & disease},

volume = {8},

number = {10},

pages = {e3100},

abstract = {MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer. Moreover, miR-34a abundance is fine-tuned by context-dependent feedback loops. The function and effects of exogenously delivered or re-expressed miR-34a on the background of defective p53 therefore remain prominent issues in miR-34a based therapy. In this work, we review p53-independent mechanisms regulating the expression of miR-34a. Aside from molecules directly interacting with MIR34A promoter, processes affecting epigenetic regulation and miRNA maturation are discussed. Multiple mechanisms operate in the context of cancer-associated phenomena, such as aberrant oncogene signaling, EMT or inflammation. Since p53-dependent tumor-suppressive mechanisms are disturbed in a substantial proportion of malignancies, we summarize the effects of miR-34a modulation in cell and animal models in the clinically relevant context of disrupted or insufficient p53 function.},

note = {Place: England},

keywords = {*Genes, Animals, Epigenesis, Epithelial-Mesenchymal Transition/genetics, Gene Expression Regulation, Genetic/genetics, Humans, MicroRNAs/*genetics, Neoplasms/*genetics/*pathology, Neoplastic/genetics, Promoter Regions, Tumor Suppressor, Tumor Suppressor Protein p53/*genetics},

pubstate = {published},

tppubtype = {article}

}

@article{soucek_fetal_2010,

title = {Fetal colon cell line FHC exhibits tumorigenic phenotype, complex karyotype, and TP53 gene mutation.},

author = {Karel Soucek and Pavla Gajdusková and Marie Brázdová and Martina Hýzd'alová and Lenka Kocí and David Vydra and Radek Trojanec and Zuzana Pernicová and Lenka Lentvorská and Marián Hajdúch and Jirina Hofmanová and Alois Kozubík},

doi = {10.1016/j.cancergencyto.2009.11.009},

issn = {1873-4456 0165-4608},

year  = {2010},

date = {2010-03-01},

journal = {Cancer genetics and cytogenetics},

volume = {197},

number = {2},

pages = {107–116},

abstract = {Stable cell lines obtained by spontaneous immortalization might represent early stages of malignant transformation and be useful experimental models for studies of mechanisms of cancer development. The FHC (fetal human cells) cell line has been established from normal fetal colonic mucosa. Detailed characterization of this cell line and mechanism of spontaneously acquired immortality have not been described yet. Therefore, we characterized the FHC cell line in terms of its tumorigenicity, cytogenetics, and TP53 gene mutation analysis. FHC cells displayed capability for anchorage-independent growth in semisolid media in vitro and formed solid tumors after transplantation into SCID (severe combined immunodeficiency) mice. This tumorigenic phenotype was associated with hypotriploidy and chromosome number ranging from 66 to 69. Results of comparative genetic hybridization arrays showed that most chromosomes included regions of copy number gains or losses. Region 8q23 approximately 8q24.3 (containing, e.g., MYC proto-oncogene) was present in more than 20 copies per nucleus. Moreover, we identified mutation of TP53 gene in codon 273; triplet CGT coding Arg was changed to CAG coding His. Expression of Pro codon 72 polymorphic variant of p53 was also detected. Mutation of TP53 gene was associated with abolished induction of p21(Waf1/Cip1) and MDM-2 proteins and resistance to apoptosis after genotoxic treatment. Because of their origin from normal fetal colon and their relative resistance to the induction of apoptosis, FHC cells can be considered a valuable experimental model for various studies.},

note = {Place: United States},

keywords = {*Genes, Animals, Apoptosis/physiology, Carcinoembryonic Antigen/metabolism, Cell Adhesion/physiology, Cell Growth Processes/physiology, Cell Line, Cell Transformation, Colon/cytology/metabolism/*physiology, Colonic Neoplasms/*genetics/*pathology, Comparative Genomic Hybridization, Cytogenetic Analysis/methods, DNA Damage, DNA Mutational Analysis/methods, Female, Fetus/cytology, Fluorescence, HCT116 Cells, Humans, In Situ Hybridization, Karyotyping, Keratins/metabolism, Mice, Neoplasm Transplantation, Neoplastic/genetics/pathology, p53, Phenotype, Proto-Oncogene Mas, SCID, Signal Transduction, Transformed},

pubstate = {published},

tppubtype = {article}

}

@article{bryja_lipoxygenase_2003,

title = {Lipoxygenase inhibitors enhance tumor suppressive effects of jun proteins on v-myb-transformed monoblasts BM2.},

author = {Vítezslav Bryja and Jirí Sedlácek and Eva Zahradnícková and Sabina Sevcíková and Jirí Pacherník and Karel Soucek and Jirina Hofmanová and Alois Kozubík and Jan Smarda},

doi = {10.1016/s1098-8823(03)00052-2},

issn = {1098-8823},

year  = {2003},

date = {2003-11-01},

journal = {Prostaglandins & other lipid mediators},

volume = {72},

number = {3-4},

pages = {131–145},

abstract = {Inhibitors of arachidonic acid (AA) conversion were described as suppressors of proliferation and inducers of differentiation of various leukemic cells. Certain AA metabolites have been shown to cooperate with Jun proteins that are important factors controlling cell proliferation, differentiation and apoptosis. Using lipoxygenase (LOX) inhibitors of various specifity we studied possible participation of lipoxygenase pathway in regulation of proliferation and apoptosis of v-myb-transformed chicken monoblasts BM2 and its functional interaction with Jun proteins. We found that nordihydroguaiaretic acid (NDGA) and esculetin (Esc) negatively regulate proliferation of BM2 cells causing accumulation in either G0/G1-phase (nordihydroguaiaretic acid) or S-phase (esculetin) of the cell cycle. BM2 cells can be also induced to undergo growth arrest and partial differentiation by ectopic expression of Jun proteins. We demonstrated that lipoxygenase inhibitors further enforce tumor suppressive capabilities of Jun proteins by inducing either more efficient cell cycle block and/or apoptosis in BM2 cells. This suggests that there is a cross-talk between the lipoxygenase- and Jun-directed pathways in regulation of differentiation and proliferation of monoblastic cells. Thus pharmacologic agents that specifically block lipoxygenase-catalyzed activity and enforce the effects of differentiation-inducers may be important components in anti-tumor therapies.},

note = {Place: United States},

keywords = {*Genes, 11, 14-Eicosatetraynoic Acid/metabolism, 5, 8, Animals, Antioxidants/pharmacology, Apoptosis, Arachidonic Acids/metabolism, Cell Cycle/drug effects, Cell Division/*drug effects, Cells, Chickens, Cultured, Humans, Lipoxygenase Inhibitors/*pharmacology, Lipoxygenase/*metabolism, Masoprocol/pharmacology, Monocytes/cytology/*drug effects/physiology, myb, Proto-Oncogene Proteins c-jun/genetics/*metabolism, Umbelliferones/pharmacology},

pubstate = {published},

tppubtype = {article}

}