Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin

Background. The non-canonical activity of retinoic acid (RA) was discovered relatively recently and consists in the rapid activation of intracellular signaling pathways by the mechanisms not related to the transcriptional activity of the RA nuclear receptors. Separate data suggest that this activity...

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Main Authors: A. D. Enikeev, A. V. Komelkov, I. B. Zborovskaya, S. A. Galetsky, G. O. Skryabin, E. M. Tchevkina
Format: Article
Language:Russian
Published: ABV-press 2019-01-01
Series:Успехи молекулярной онкологии
Subjects:
Online Access:https://umo.abvpress.ru/jour/article/view/182
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author A. D. Enikeev
A. V. Komelkov
I. B. Zborovskaya
S. A. Galetsky
G. O. Skryabin
E. M. Tchevkina
author_facet A. D. Enikeev
A. V. Komelkov
I. B. Zborovskaya
S. A. Galetsky
G. O. Skryabin
E. M. Tchevkina
author_sort A. D. Enikeev
collection DOAJ
description Background. The non-canonical activity of retinoic acid (RA) was discovered relatively recently and consists in the rapid activation of intracellular signaling pathways by the mechanisms not related to the transcriptional activity of the RA nuclear receptors. Separate data suggest that this activity can stimulate the processes of malignancy and contribute to the formation of tumor cell resistance to RA as a therapeutic agent. However, little is known about the mechanisms of this activity. It is also unclear how universal this effect is; does the RA-dependent activation of different signaling protein kinases occur in the same cells, and whether activation of these kinases is interrelated.Materials and methods: cultivation of non-small cell lung cancer cells and neuroblastoma cells under standard conditions and with incubation with all-trans retinoic acid (ATRA); immunoblotting.Results. Here we studied the effect of ATRA on the activation of Akt and Erk1/2 protein kinases depending on the incubation time. The analysis revealed RA-dependent activation of both kinases in all studied non-small cell lung cancer and neuroblastoma cell lines. Activation of Akt and Erk1/2 occurred at five minutes of incubation, which corresponds to the non-transcriptional (non-canonical) activity of the RA, however, further activation kinetics of the two kinases differed essentially.Conclusion. We found that ATRA causes rapid activation of Erk1/2 and Akt protein kinases in both non-small cell lung cancer and neuroblastoma cells. The differences in the kinetics of RA-dependent stimulation of these two kinases suggest that their activation is mediated by independent mechanisms.
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spelling doaj.art-e1464ade1a3d4ec1bece402d74f948da2023-09-03T09:14:41ZrusABV-pressУспехи молекулярной онкологии2313-805X2413-37872019-01-015412713010.17650/2313-805X-2018-5-4-127-130146Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different originA. D. Enikeev0A. V. Komelkov1I. B. Zborovskaya2S. A. Galetsky3G. O. Skryabin4E. M. Tchevkina5НИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииНИИ канцерогенеза, ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииBackground. The non-canonical activity of retinoic acid (RA) was discovered relatively recently and consists in the rapid activation of intracellular signaling pathways by the mechanisms not related to the transcriptional activity of the RA nuclear receptors. Separate data suggest that this activity can stimulate the processes of malignancy and contribute to the formation of tumor cell resistance to RA as a therapeutic agent. However, little is known about the mechanisms of this activity. It is also unclear how universal this effect is; does the RA-dependent activation of different signaling protein kinases occur in the same cells, and whether activation of these kinases is interrelated.Materials and methods: cultivation of non-small cell lung cancer cells and neuroblastoma cells under standard conditions and with incubation with all-trans retinoic acid (ATRA); immunoblotting.Results. Here we studied the effect of ATRA on the activation of Akt and Erk1/2 protein kinases depending on the incubation time. The analysis revealed RA-dependent activation of both kinases in all studied non-small cell lung cancer and neuroblastoma cell lines. Activation of Akt and Erk1/2 occurred at five minutes of incubation, which corresponds to the non-transcriptional (non-canonical) activity of the RA, however, further activation kinetics of the two kinases differed essentially.Conclusion. We found that ATRA causes rapid activation of Erk1/2 and Akt protein kinases in both non-small cell lung cancer and neuroblastoma cells. The differences in the kinetics of RA-dependent stimulation of these two kinases suggest that their activation is mediated by independent mechanisms.https://umo.abvpress.ru/jour/article/view/182ретиноевая кислотанеканоническая активностьпротеинкиназафосфорилированиеerk1/2akt
spellingShingle A. D. Enikeev
A. V. Komelkov
I. B. Zborovskaya
S. A. Galetsky
G. O. Skryabin
E. M. Tchevkina
Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
Успехи молекулярной онкологии
ретиноевая кислота
неканоническая активность
протеинкиназа
фосфорилирование
erk1/2
akt
title Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
title_full Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
title_fullStr Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
title_full_unstemmed Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
title_short Non-canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
title_sort non canonical activity of retinoic acid in relation to the activation of protein kinases in transformed cells of different origin
topic ретиноевая кислота
неканоническая активность
протеинкиназа
фосфорилирование
erk1/2
akt
url https://umo.abvpress.ru/jour/article/view/182
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AT ibzborovskaya noncanonicalactivityofretinoicacidinrelationtotheactivationofproteinkinasesintransformedcellsofdifferentorigin
AT sagaletsky noncanonicalactivityofretinoicacidinrelationtotheactivationofproteinkinasesintransformedcellsofdifferentorigin
AT goskryabin noncanonicalactivityofretinoicacidinrelationtotheactivationofproteinkinasesintransformedcellsofdifferentorigin
AT emtchevkina noncanonicalactivityofretinoicacidinrelationtotheactivationofproteinkinasesintransformedcellsofdifferentorigin