2011
Slabáková, Eva; Pernicová, Zuzana; Slavíčková, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel
TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Journal Article
In: The Prostate, vol. 71, no. 12, pp. 1332–1343, 2011, ISSN: 1097-0045 0270-4137, (Place: United States).
Abstract | Links | BibTeX | Tags: *Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1
@article{slabakova_tgf-1-induced_2011,
title = {TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug.},
author = {Eva Slabáková and Zuzana Pernicová and Eva Slavíčková and Andrea Staršíchová and Alois Kozubík and Karel Souček},
doi = {10.1002/pros.21350},
issn = {1097-0045 0270-4137},
year = {2011},
date = {2011-09-01},
journal = {The Prostate},
volume = {71},
number = {12},
pages = {1332–1343},
abstract = {BACKGROUND: Epithelial-mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described. METHODS: EMT in BPH-1 cells was induced by TGF-β1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT-PCR. RESULTS: EMT in BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR-200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH-1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR-200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF-β1-induced vimentin up-regulation and migration of BPH-1 cells. CONCLUSIONS: This study suggests that in BPH-1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR-200 family may oppose the reversal of the EMT phenotype.},
note = {Place: United States},
keywords = {*Epithelial-Mesenchymal Transition/genetics, Biomarkers/metabolism, Cell Line, Cell Movement, Homeodomain Proteins/genetics, Humans, Kinetics, Male, Messenger/metabolism, MicroRNAs/metabolism, Neoplasm Invasiveness/genetics, Phenotype, Prostatic Hyperplasia/*physiopathology, Repressor Proteins/genetics, RNA, Snail Family Transcription Factors, Transcription Factors/*biosynthesis/genetics, Transforming Growth Factor beta1/*pharmacology, Up-Regulation/drug effects, Vimentin/metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Epithelial-mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described. METHODS: EMT in BPH-1 cells was induced by TGF-β1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT-PCR. RESULTS: EMT in BPH-1 cells was accompanied by rapid up-regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR-200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH-1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR-200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF-β1-induced vimentin up-regulation and migration of BPH-1 cells. CONCLUSIONS: This study suggests that in BPH-1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR-200 family may oppose the reversal of the EMT phenotype.
Pernicová, Zuzana; Slabáková, Eva; Kharaishvili, Gvantsa; Bouchal, Jan; Král, Milan; Kunická, Zuzana; Machala, Miroslav; Kozubík, Alois; Souček, Karel
Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Journal Article
In: Neoplasia (New York, N.Y.), vol. 13, no. 6, pp. 526–536, 2011, ISSN: 1476-5586 1522-8002, (Place: United States).
Abstract | Links | BibTeX | Tags: Androgen Antagonists/*pharmacology, Androgen/metabolism, beta-Galactosidase/metabolism, Blotting, Cathepsin B/metabolism, Cell Line, Cellular Senescence/*drug effects, Confocal, Down-Regulation/*drug effects, Flow Cytometry, Humans, Insulin-Like Growth Factor Binding Protein 3/metabolism, Male, Microscopy, Prostatic Neoplasms/genetics/metabolism/pathology, PTEN Phosphohydrolase/metabolism, Receptors, RNA Interference, S-Phase Kinase-Associated Proteins/genetics/*metabolism, Signal Transduction/drug effects, Tumor, Vimentin/metabolism, Western
@article{pernicova_androgen_2011,
title = {Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2.},
author = {Zuzana Pernicová and Eva Slabáková and Gvantsa Kharaishvili and Jan Bouchal and Milan Král and Zuzana Kunická and Miroslav Machala and Alois Kozubík and Karel Souček},
doi = {10.1593/neo.11182},
issn = {1476-5586 1522-8002},
year = {2011},
date = {2011-06-01},
journal = {Neoplasia (New York, N.Y.)},
volume = {13},
number = {6},
pages = {526–536},
abstract = {Although the induction of senescence in cancer cells is a potent mechanism of tumor suppression, senescent cells remain metabolically active and may secrete a broad spectrum of factors that promote tumorigenicity in neighboring malignant cells. Here we show that androgen deprivation therapy (ADT), a widely used treatment for advanced prostate cancer, induces a senescence-associated secretory phenotype in prostate cancer epithelial cells, indicated by increases in senescence-associated β-galactosidase activity, heterochromatin protein 1β foci, and expression of cathepsin B and insulin-like growth factor binding protein 3. Interestingly, ADT also induced high levels of vimentin expression in prostate cancer cell lines in vitro and in human prostate tumors in vivo. The induction of the senescence-associated secretory phenotype by androgen depletion was mediated, at least in part, by down-regulation of S-phase kinase-associated protein 2, whereas the neuroendocrine differentiation of prostate cancer cells was under separate control. These data demonstrate a previously unrecognized link between inhibition of androgen receptor signaling, down-regulation of S-phase kinase-associated protein 2, and the appearance of secretory, tumor-promoting senescent cells in prostate tumors. We propose that ADT may contribute to the development of androgen-independent prostate cancer through modulation of the tissue microenvironment by senescent cells.},
note = {Place: United States},
keywords = {Androgen Antagonists/*pharmacology, Androgen/metabolism, beta-Galactosidase/metabolism, Blotting, Cathepsin B/metabolism, Cell Line, Cellular Senescence/*drug effects, Confocal, Down-Regulation/*drug effects, Flow Cytometry, Humans, Insulin-Like Growth Factor Binding Protein 3/metabolism, Male, Microscopy, Prostatic Neoplasms/genetics/metabolism/pathology, PTEN Phosphohydrolase/metabolism, Receptors, RNA Interference, S-Phase Kinase-Associated Proteins/genetics/*metabolism, Signal Transduction/drug effects, Tumor, Vimentin/metabolism, Western},
pubstate = {published},
tppubtype = {article}
}
Although the induction of senescence in cancer cells is a potent mechanism of tumor suppression, senescent cells remain metabolically active and may secrete a broad spectrum of factors that promote tumorigenicity in neighboring malignant cells. Here we show that androgen deprivation therapy (ADT), a widely used treatment for advanced prostate cancer, induces a senescence-associated secretory phenotype in prostate cancer epithelial cells, indicated by increases in senescence-associated β-galactosidase activity, heterochromatin protein 1β foci, and expression of cathepsin B and insulin-like growth factor binding protein 3. Interestingly, ADT also induced high levels of vimentin expression in prostate cancer cell lines in vitro and in human prostate tumors in vivo. The induction of the senescence-associated secretory phenotype by androgen depletion was mediated, at least in part, by down-regulation of S-phase kinase-associated protein 2, whereas the neuroendocrine differentiation of prostate cancer cells was under separate control. These data demonstrate a previously unrecognized link between inhibition of androgen receptor signaling, down-regulation of S-phase kinase-associated protein 2, and the appearance of secretory, tumor-promoting senescent cells in prostate tumors. We propose that ADT may contribute to the development of androgen-independent prostate cancer through modulation of the tissue microenvironment by senescent cells.