Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects
Aim: About 30–40% of breast cancers lack steroid receptors (ER and/or PR) at diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim of this paper has been to study the role of DNA-damaging factors as the potential modifiers of the receptor-negative tumors incidence. Material...
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| Дата: | 2006 |
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| Автори: | , , , , , , |
| Формат: | Стаття |
| Мова: | English |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2006
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| Назва видання: | Experimental Oncology |
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| Онлайн доступ: | http://dspace.nbuv.gov.ua/handle/123456789/134529 |
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| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects / L.M. Berstein, E.V. Tsyrlina, T.E. Poroshina, V.V. Levina, D.A. Vasilyev, I.G. Kovalenko, V.F. Semiglazov // Experimental Oncology. — 2006. — Т. 28, № 1. — С. 64-69. — Бібліогр.: 32 назв. — англ. |
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Original contributions Original contributions |
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Original contributions Original contributions Berstein, L.M. Tsyrlina, E.V. Poroshina, T.E. Levina, V.V. Vasilyev, D.A. Kovalenko, I.G. Semiglazov, V.F. Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects Experimental Oncology |
| description |
Aim: About 30–40% of breast cancers lack steroid receptors (ER and/or PR) at diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim of this paper has been to study the role of DNA-damaging factors as the potential modifiers of the receptor-negative tumors incidence. Materials and Methods: The investigation consisted of two principal parts. In one of them ER and PR content was measured in breast cancer samples from 2284 primary patients (350 of them — current or previous smokers). In separately studied subgroup of 1010 patients 95 suffered with diabetes mellitus type II. Results: As it was shown, smokers and diabetics carry more frequently (p < 0.05) tumors with phenotypes ER+PR- and PR- only in the group of women with conserved menstrual cycle that is in case of relatively higher estrogenic stimulation. In another part of the investigation immunohistochemical study of DNA damage marker — 8-hydroxy-2-deoxyguanosine (8-OH-dG) in 16 R(-) and 18 R(+) breast cancer specimens demonstrated more frequent positive staining in the former group of samples (p = 0.05). Besides, as it was revealed in breast cancer cell line MCF-7 the combination of estradiol with aryl hydrocarbonic receptors agonist beta-naphtoflavone induced pronounced genotoxic damage (by 8-OH-dG content) in association with the loss of ER. Conclusion: Thus, pro-genotoxic status (smoking, diabetes) and direct signs of genotoxic injury, in accordance with regularities of the phenomenon of switching of estrogen effects.
can be reckoned among the factors promoting the development of receptor-negative breast cancer. |
| format |
Article |
| author |
Berstein, L.M. Tsyrlina, E.V. Poroshina, T.E. Levina, V.V. Vasilyev, D.A. Kovalenko, I.G. Semiglazov, V.F. |
| author_facet |
Berstein, L.M. Tsyrlina, E.V. Poroshina, T.E. Levina, V.V. Vasilyev, D.A. Kovalenko, I.G. Semiglazov, V.F. |
| author_sort |
Berstein, L.M. |
| title |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| title_short |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| title_full |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| title_fullStr |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| title_full_unstemmed |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| title_sort |
genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2006 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/134529 |
| citation_txt |
Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects / L.M. Berstein, E.V. Tsyrlina, T.E. Poroshina, V.V. Levina, D.A. Vasilyev, I.G. Kovalenko, V.F. Semiglazov // Experimental Oncology. — 2006. — Т. 28, № 1. — С. 64-69. — Бібліогр.: 32 назв. — англ. |
| series |
Experimental Oncology |
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irk-123456789-1345292018-06-14T03:06:30Z Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects Berstein, L.M. Tsyrlina, E.V. Poroshina, T.E. Levina, V.V. Vasilyev, D.A. Kovalenko, I.G. Semiglazov, V.F. Original contributions Aim: About 30–40% of breast cancers lack steroid receptors (ER and/or PR) at diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim of this paper has been to study the role of DNA-damaging factors as the potential modifiers of the receptor-negative tumors incidence. Materials and Methods: The investigation consisted of two principal parts. In one of them ER and PR content was measured in breast cancer samples from 2284 primary patients (350 of them — current or previous smokers). In separately studied subgroup of 1010 patients 95 suffered with diabetes mellitus type II. Results: As it was shown, smokers and diabetics carry more frequently (p < 0.05) tumors with phenotypes ER+PR- and PR- only in the group of women with conserved menstrual cycle that is in case of relatively higher estrogenic stimulation. In another part of the investigation immunohistochemical study of DNA damage marker — 8-hydroxy-2-deoxyguanosine (8-OH-dG) in 16 R(-) and 18 R(+) breast cancer specimens demonstrated more frequent positive staining in the former group of samples (p = 0.05). Besides, as it was revealed in breast cancer cell line MCF-7 the combination of estradiol with aryl hydrocarbonic receptors agonist beta-naphtoflavone induced pronounced genotoxic damage (by 8-OH-dG content) in association with the loss of ER. Conclusion: Thus, pro-genotoxic status (smoking, diabetes) and direct signs of genotoxic injury, in accordance with regularities of the phenomenon of switching of estrogen effects. can be reckoned among the factors promoting the development of receptor-negative breast cancer. Цель исследования: примерно в 30–40% случаев рака молочной железы (РМЖ) рецепторы стероидных гормонов (ЭР и/или ПР) не выявлены, что оказывает неблагоприятное влияние на прогноз заболевания и ограничивает применение гормонотерапии. Задачей настоящей работы было изучение роли факторов, ассоциированных с повреждением ДНК, как потенциальных модификаторов частоты возникновения рецепторнегативных новообразований. Материалы и методы: исследование состояло из двух основных частей. У 2284 первичных больных РМЖ (350 из них — курящие или курившие ранее) содержание ЭР и ПР в опухолевой ткани определяли рецепторным методом. В отдельно проанализированной подгруппе из 1010 больных у 95 пациенток диагностировали сахарный диабет ІІ типа. Результаты: установлено, что в отличие от пациенток в постменопаузальный период с сохраненной менструальной функцией (то есть в условиях более высокой эстрогенной стимуляции) отмечается достоверное преобладание опухолей фенотипа ЭР + ПР — у курящих по сравнению с некурящими (t = 2,18, p < 0,05), а также у больных сахарным диабетом по сравнению с больными без него (t = 2,01, p = 0,05). Кроме того, в репродуктивный период у больных сахарным диабетом доля ПР(-)-опухолей достоверно превосходила таковую у пациенток без него (t = 2,17, p < 0,05). Во второй части исследования с помощью иммуногис- тохимического метода изучено содержание показателя повреждения ДНК 8-гидрокси-2-дезоксигуанозина (8-OH-dG) в 16 рецепторнегативных и 18 рецепторпозитивных опухолях молочной железы. Выявлено, что в первой группе позитивное окрашивание наблюдали в 81,3 ± 9,8%, а во второй — в 50,0 ± 11,7% случаев, p = 0,05. Помимо этого, результаты экспе- римента на клеточной линии МСF-7 рака молочной железы свидетельствуют, что при комбинации эстрадиола с агонистом арилгидрокарбоновых рецепторов бета-нафтофлавоном значительное усиление генотоксического повреждения (по данным определения 8-ОН-dG) отмечается уже к 60 мин эксперимента, когда выявляют и снижение концентрации ЭР. Выводы: прегенотоксический статус (курение, сахарный диабет), равно как и признаки прямого генотоксического повреждения, в соответствии с представлениями о феномене переключения эстрогенного эффекта могут быть причислены к факторам, способствующим развитию рецепторнегативного РМЖ. 2006 Article Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects / L.M. Berstein, E.V. Tsyrlina, T.E. Poroshina, V.V. Levina, D.A. Vasilyev, I.G. Kovalenko, V.F. Semiglazov // Experimental Oncology. — 2006. — Т. 28, № 1. — С. 64-69. — Бібліогр.: 32 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/134529 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |