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8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor

The growth factor-activated mitogenic pathways are often disregulated in tumour cells and, therefore, they can provide specific molecular targets for novel anti-tumour approaches. 8-Chloro-cAMP (8-Cl-cAMP), a synthetic cAMP analogue, is a novel anti-tumour agent that has recently undergone clinical...

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Autores principales: Budillon, A, Gennaro, E Di, Caraglia, M, Barbarulo, D, Abbruzzese, A, Tagliaferri, P
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374321/
https://www.ncbi.nlm.nih.gov/pubmed/10584873
http://dx.doi.org/10.1038/sj.bjc.6690820
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author Budillon, A
Gennaro, E Di
Caraglia, M
Barbarulo, D
Abbruzzese, A
Tagliaferri, P
author_facet Budillon, A
Gennaro, E Di
Caraglia, M
Barbarulo, D
Abbruzzese, A
Tagliaferri, P
author_sort Budillon, A
collection PubMed
description The growth factor-activated mitogenic pathways are often disregulated in tumour cells and, therefore, they can provide specific molecular targets for novel anti-tumour approaches. 8-Chloro-cAMP (8-Cl-cAMP), a synthetic cAMP analogue, is a novel anti-tumour agent that has recently undergone clinical evaluation. We investigated the effects of 8-CI-cAMP on the epidermal growth factor (EGF)/EGF receptor (EGF-R) signalling in human epidermoid cancer KB cells, which are responsive to the mitogenic stimulus of EGF. We found that the growth-promoting activity of EGF was completely abolished when EGF treatment was performed in combination with 8-CI-cAMP. The inhibition of the EGF-induced proliferation by 8-CI-cAMP was paralleled by the blockade of the EGF-stimulated activation of mitogen-activated protein kinases (MAPK), ERK-1 and ERK-2. Conversely, we found an increase of EGF-R expression and EGF-R tyrosine phosphorylation when KB cells were growth inhibited by 8-Cl-cAMP. Moreover, the activity of Raf-1 and MEK-1 protein kinases, the activators upstream MAPK in the phosphorylation cascade induced by EGF, was not modified in 8-Cl-cAMP-treated cells. We concluded that the impairment of KB cell response to EGF, induced by 8-Cl-cAMP, resides in the specific inhibition of MAPK/ERKs activity while the function of the upstream elements in the EGF-R signalling is preserved. © 1999 Cancer Research Campaign
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spelling pubmed-23743212009-09-10 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor Budillon, A Gennaro, E Di Caraglia, M Barbarulo, D Abbruzzese, A Tagliaferri, P Br J Cancer Regular Article The growth factor-activated mitogenic pathways are often disregulated in tumour cells and, therefore, they can provide specific molecular targets for novel anti-tumour approaches. 8-Chloro-cAMP (8-Cl-cAMP), a synthetic cAMP analogue, is a novel anti-tumour agent that has recently undergone clinical evaluation. We investigated the effects of 8-CI-cAMP on the epidermal growth factor (EGF)/EGF receptor (EGF-R) signalling in human epidermoid cancer KB cells, which are responsive to the mitogenic stimulus of EGF. We found that the growth-promoting activity of EGF was completely abolished when EGF treatment was performed in combination with 8-CI-cAMP. The inhibition of the EGF-induced proliferation by 8-CI-cAMP was paralleled by the blockade of the EGF-stimulated activation of mitogen-activated protein kinases (MAPK), ERK-1 and ERK-2. Conversely, we found an increase of EGF-R expression and EGF-R tyrosine phosphorylation when KB cells were growth inhibited by 8-Cl-cAMP. Moreover, the activity of Raf-1 and MEK-1 protein kinases, the activators upstream MAPK in the phosphorylation cascade induced by EGF, was not modified in 8-Cl-cAMP-treated cells. We concluded that the impairment of KB cell response to EGF, induced by 8-Cl-cAMP, resides in the specific inhibition of MAPK/ERKs activity while the function of the upstream elements in the EGF-R signalling is preserved. © 1999 Cancer Research Campaign Nature Publishing Group 1999-12 /pmc/articles/PMC2374321/ /pubmed/10584873 http://dx.doi.org/10.1038/sj.bjc.6690820 Text en Copyright © 1999 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Budillon, A
Gennaro, E Di
Caraglia, M
Barbarulo, D
Abbruzzese, A
Tagliaferri, P
8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title_full 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title_fullStr 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title_full_unstemmed 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title_short 8-Cl-cAMP antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
title_sort 8-cl-camp antagonizes mitogen-activated protein kinase activation and cell growth stimulation induced by epidermal growth factor
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374321/
https://www.ncbi.nlm.nih.gov/pubmed/10584873
http://dx.doi.org/10.1038/sj.bjc.6690820
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