Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines

Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines

Aim: The impact of combinations of anti-cancer drugs and growth factors on tumour cells may differ from the assumed sum of the effects of each factor separately. Therefore it is important to study the effects of different combinations of various drugs and treatments. Our aim was to study the effects...

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Published in:Experimental Oncology
Date:2014
Main Authors: Mints, M., Souchelnytskyi, S.
Format: Article
Language:English
Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2014
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Online Access:https://nasplib.isofts.kiev.ua/handle/123456789/145334
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Journal Title:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Cite this:Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines / M. Mints, S. Souchelnytskyi // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 67-71. — Бібліогр.: 20 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
id nasplib_isofts_kiev_ua-123456789-145334
record_format dspace
spelling Mints, M.
Souchelnytskyi, S.
2019-01-20T16:22:05Z
2019-01-20T16:22:05Z
2014
Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines / M. Mints, S. Souchelnytskyi // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 67-71. — Бібліогр.: 20 назв. — англ.
1812-9269
https://nasplib.isofts.kiev.ua/handle/123456789/145334
Aim: The impact of combinations of anti-cancer drugs and growth factors on tumour cells may differ from the assumed sum of the effects of each factor separately. Therefore it is important to study the effects of different combinations of various drugs and treatments. Our aim was to study the effects on breast cancer cell proliferation of EGF, TGFβ and 17β-oestradiol, three important regulators of breast tumourigenesis, and their respective inhibitors in different combinations. Materials and Methods: We screened the effects on proliferation of MCF7 and MDA-MB-231 cells of ninety different combinations of EGF, TGFβ and 17β-oestradiol, Iressa, SB431542 and Tamoxifen. Meta-data analysis of available clinical data was performed to validate observed proliferation data. Results: In MDA-MB-231 cells, TGFβ1 was found inhibitory when cells were simultaneously treated with EGF and 17β-oestradiol, with the effect potentiated by addition of all inhibitors combined. In the same cells, Iressa when combined with EGF was paradoxically stimulatory. Tamoxifen inhibited MCF7 cells co-treated with EGF or oestrogen, and enhanced the inhibitory effect of TGFβ in MDA-MB-231 cells. Meta-analysis of clinical gene expression studies confirmed several of these points, showing enhanced TGFβ and EGF expression in Tamoxifen-treated patients to correlate with decreased tumour size and grade respectively, and combined TGFβ-EGF expression to decrease the risk of metastasis. Conclusion: Our study shows significant differences in proliferation response to drugs and growth factors between MCF7 cells which do not have propensity to form metastases in animal models and MDA-MB-231 cells which may form metastases upon inoculation into animals. Several of these differences are unexpected and confirmed by clinical observations. Key Words: breast cancer, combinatorial treatment, EGF, oestrogen, TGFβ.
We are grateful to the Oves Minnesfond for support and encouragement. This work is supported in part by grants from the Radiumhemmet research funds (№ 121202), the Swedish Cancer Society, the Swedish Research Council, the Swedish Institute, INTAS, Erasmus KI-UWM and STINT to S.S., and by MD/PhD program to M.M.
en
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
Experimental Oncology
Original contributions
Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
Article
published earlier
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
title Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
spellingShingle Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
Mints, M.
Souchelnytskyi, S.
Original contributions
title_short Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
title_full Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
title_fullStr Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
title_full_unstemmed Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
title_sort impact of combinations of egf, tgfβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines
author Mints, M.
Souchelnytskyi, S.
author_facet Mints, M.
Souchelnytskyi, S.
topic Original contributions
topic_facet Original contributions
publishDate 2014
language English
container_title Experimental Oncology
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
format Article
description Aim: The impact of combinations of anti-cancer drugs and growth factors on tumour cells may differ from the assumed sum of the effects of each factor separately. Therefore it is important to study the effects of different combinations of various drugs and treatments. Our aim was to study the effects on breast cancer cell proliferation of EGF, TGFβ and 17β-oestradiol, three important regulators of breast tumourigenesis, and their respective inhibitors in different combinations. Materials and Methods: We screened the effects on proliferation of MCF7 and MDA-MB-231 cells of ninety different combinations of EGF, TGFβ and 17β-oestradiol, Iressa, SB431542 and Tamoxifen. Meta-data analysis of available clinical data was performed to validate observed proliferation data. Results: In MDA-MB-231 cells, TGFβ1 was found inhibitory when cells were simultaneously treated with EGF and 17β-oestradiol, with the effect potentiated by addition of all inhibitors combined. In the same cells, Iressa when combined with EGF was paradoxically stimulatory. Tamoxifen inhibited MCF7 cells co-treated with EGF or oestrogen, and enhanced the inhibitory effect of TGFβ in MDA-MB-231 cells. Meta-analysis of clinical gene expression studies confirmed several of these points, showing enhanced TGFβ and EGF expression in Tamoxifen-treated patients to correlate with decreased tumour size and grade respectively, and combined TGFβ-EGF expression to decrease the risk of metastasis. Conclusion: Our study shows significant differences in proliferation response to drugs and growth factors between MCF7 cells which do not have propensity to form metastases in animal models and MDA-MB-231 cells which may form metastases upon inoculation into animals. Several of these differences are unexpected and confirmed by clinical observations. Key Words: breast cancer, combinatorial treatment, EGF, oestrogen, TGFβ.
issn 1812-9269
url https://nasplib.isofts.kiev.ua/handle/123456789/145334
citation_txt Impact of combinations of EGF, TGFβ, 17β-oestradiol, and inhibitors of corresponding pathways on proliferation of breast cancer cell lines / M. Mints, S. Souchelnytskyi // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 67-71. — Бібліогр.: 20 назв. — англ.
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AT souchelnytskyis impactofcombinationsofegftgfβ17βoestradiolandinhibitorsofcorrespondingpathwaysonproliferationofbreastcancercelllines
first_indexed 2025-12-01T14:51:34Z
last_indexed 2025-12-01T14:51:34Z
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