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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| Опубліковано в: : | Experimental Oncology |
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| Дата: | 2014 |
| Автори: | , |
| Формат: | Стаття |
| Мова: | Англійська |
| Опубліковано: |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2014
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| Онлайн доступ: | https://nasplib.isofts.kiev.ua/handle/123456789/145334 |
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| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | 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. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1862649011830259712 |
|---|---|
| author | Mints, M. Souchelnytskyi, S. |
| author_facet | Mints, M. Souchelnytskyi, S. |
| 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. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| 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.
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| first_indexed | 2025-12-01T14:51:34Z |
| format | Article |
| fulltext | |
| id | nasplib_isofts_kiev_ua-123456789-145334 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-01T14:51:34Z |
| publishDate | 2014 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| 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 |
| 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 | 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_short | 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 |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145334 |
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