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Open AccessArticle

Induction of Urokinase Activity by Retinoic Acid in Two Cell Lines of Neuronal Origin

1
Department of Molecular Biology, Faculty of Science, University of Zagreb, Horvatovac 102A, 10000 Zagreb, Croatia
2
Division of Molecular Biology, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(3), 70; https://doi.org/10.3390/biomedicines7030070
Received: 19 July 2019 / Revised: 10 September 2019 / Accepted: 11 September 2019 / Published: 12 September 2019
Retinoic acid is one of the most well-known agents able to induce differentiation in several types of tumours. Unfortunately, most of the tumours are refractive to the differentiation cues. The aim of this investigation was to analyse the effects of prolonged treatment with retinoic acid on two cell lines of neural origin refractive to differentiation. Cells were also treated with retinoic acid in combination with a poly(ADP-ribosyl) polymerase (PARP) inhibitor because PARP1 is a known chromatin modulator and can influence the process of differentiation. The main methods comprised tumour cell line culturing and treatment; analysis of RNA and protein expression after cell treatment; as well as analysis of urokinase activity, migration, and proliferation. Both cell lines continued to proliferate under the prolonged treatment and showed increase in urokinase plasminogen activator activity. Analysis of gene expression and cell phenotype revealed different mechanisms, which only in neuroblastoma H4 cells could indicate the process of epithelial-mesenchymal transition. The data collected indicate that the activity of the urokinase plasminogen activator, although belonging to an extracellular protease, does not necessary lead to epithelial-mesenchymal reprogramming and increase in cell migration but can have different outcomes depending on the intracellular milieu. View Full-Text
Keywords: neuroglioblastoma cell line; glioblastoma; retinoic acid; PARP1; urokinase; epithelial-mesenchymal transition neuroglioblastoma cell line; glioblastoma; retinoic acid; PARP1; urokinase; epithelial-mesenchymal transition
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MDPI and ACS Style

Horvat, L.; Madunić, J.; Grubar, M.; Antica, M.; Matulić, M. Induction of Urokinase Activity by Retinoic Acid in Two Cell Lines of Neuronal Origin. Biomedicines 2019, 7, 70.

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