Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells
Аутори
Petrović, IsidoraMilivojević, Milena
Arsenijević, Ana
Lazić, Andrijana
Kovačević Grujičić, Nataša
Schwirtlich, Marija
Popović, Jelena
Stevanović, Milena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent, on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits c...ell growth, reduces the number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.
Кључне речи:
Transcription factors / SK-BR-3 cell line / MCF7 cell line / Breast carcinoma / Anti-proliferative activityИзвор:
Biocell, 2021, 45, 5, 1355-1367Издавач:
- Tech Science Press, Henderson
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200042 (Универзитет у Београду, Институт за молекуларну генетику и генетичко инжењерство) (RS-MESTD-inst-2020-200042)
- Serbian Academy of Sciences and Arts
DOI: 10.32604/biocell.2021.015817
ISSN: 0327-9545
WoS: 000672801900017
Scopus: 2-s2.0-85111989060
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Petrović, Isidora AU - Milivojević, Milena AU - Arsenijević, Ana AU - Lazić, Andrijana AU - Kovačević Grujičić, Nataša AU - Schwirtlich, Marija AU - Popović, Jelena AU - Stevanović, Milena PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1505 AB - Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent, on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits cell growth, reduces the number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes. PB - Tech Science Press, Henderson T2 - Biocell T1 - Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells EP - 1367 IS - 5 SP - 1355 VL - 45 DO - 10.32604/biocell.2021.015817 ER -
@article{ author = "Petrović, Isidora and Milivojević, Milena and Arsenijević, Ana and Lazić, Andrijana and Kovačević Grujičić, Nataša and Schwirtlich, Marija and Popović, Jelena and Stevanović, Milena", year = "2021", abstract = "Genetic and molecular heterogeneity, together with intrinsic and acquired resistance to therapy, represent the major obstacles to the successful treatment of different types of breast carcinoma. Increasing evidence demonstrates that SOX transcription factors in breast carcinomas could act both as oncogenes and tumor suppressors and have been associated with tumor stage and grade, poor prognosis, and therapy resistance. Both SOX2 and SOX18 overexpression has been correlated with poor prognosis in breast carcinomas, and these genes are recognized as potential antitumor targets. Our aim was to evaluate the effect of retinoic acid (RA), a well-known cyto-differentiating agent, on breast carcinoma cells in vitro and to investigate the potential of RA treatment to modify the expression of SOX2 and SOX18 genes. By applying various experimental approaches, we evaluated the effect of RA on basic cellular processes in SK-BR-3 and MCF7 breast carcinoma cell lines. We have shown that RA inhibits cell growth, reduces the number of Ki-67 positive cells, and causes cell-cycle arrest. RA effect was more prominent in SK-BR-3 cell line that lacks SOX2 expression, including a higher decrease in cell viability, reduction in colony formation, and significant remodeling of cellular structure. We have shown that RA treatment led to the downregulation of SOX2 expression in MCF7 cells and to the reduction of SOX18 expression in both cell lines. By functional analysis, we showed that the anti-proliferative effect of RA in both cell lines was not based on the activity of stemness marker SOX2, pointing to a SOX2-independent mechanism of action. The ability of RA to reduce SOX2/SOX18 expression raises the possibility that these genes can be used as biomarkers to distinguish RA-responders from non-responders. Together, our study shows that the response of breast carcinoma cell lines to RA treatment may vary, highlighting that the development of RA-based therapy should consider differences in breast carcinoma subtypes.", publisher = "Tech Science Press, Henderson", journal = "Biocell", title = "Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells", pages = "1367-1355", number = "5", volume = "45", doi = "10.32604/biocell.2021.015817" }
Petrović, I., Milivojević, M., Arsenijević, A., Lazić, A., Kovačević Grujičić, N., Schwirtlich, M., Popović, J.,& Stevanović, M.. (2021). Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells. in Biocell Tech Science Press, Henderson., 45(5), 1355-1367. https://doi.org/10.32604/biocell.2021.015817
Petrović I, Milivojević M, Arsenijević A, Lazić A, Kovačević Grujičić N, Schwirtlich M, Popović J, Stevanović M. Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells. in Biocell. 2021;45(5):1355-1367. doi:10.32604/biocell.2021.015817 .
Petrović, Isidora, Milivojević, Milena, Arsenijević, Ana, Lazić, Andrijana, Kovačević Grujičić, Nataša, Schwirtlich, Marija, Popović, Jelena, Stevanović, Milena, "Retinoic acid affects basic cellular processes and SOX2 and SOX18 expression in breast carcinoma cells" in Biocell, 45, no. 5 (2021):1355-1367, https://doi.org/10.32604/biocell.2021.015817 . .