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Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines
OBJECTIVE: Chromosomal instability (CIN) is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes, frequently observed in cancer cell populations and is associated with poor prognosis, metastasis, and therapeutic resistance. Breast cancer (BC) is ch...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Compuscript
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721098/ https://www.ncbi.nlm.nih.gov/pubmed/33299647 http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0028 |
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author | Vargas-Rondón, Natalia Pérez-Mora, Erika Villegas, Victoria E. Rondón-Lagos, Milena |
author_facet | Vargas-Rondón, Natalia Pérez-Mora, Erika Villegas, Victoria E. Rondón-Lagos, Milena |
author_sort | Vargas-Rondón, Natalia |
collection | PubMed |
description | OBJECTIVE: Chromosomal instability (CIN) is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes, frequently observed in cancer cell populations and is associated with poor prognosis, metastasis, and therapeutic resistance. Breast cancer (BC) is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens. However, paradoxical associations between extreme CIN and improved outcome have been observed. METHODS: This study aimed to 1) evaluate CIN levels and clonal heterogeneity (CH) in MCF7, ZR-751, MDA-MB468, BT474, and KPL4 BC cells treated with low doses of tamoxifen (TAM), docetaxel (DOC), doxorubicin (DOX), Herceptin (HT), and combined treatments (TAM/DOC, TAM/DOX, TAM/HT, HT/DOC, and HT/DOX) by using fluorescence in situ hybridization (FISH), and 2) examine the association with response to treatments by comparing FISH results with cell proliferation. RESULTS: Intermediate CIN was linked to drug sensitivity according to three characteristics: estrogen receptor α (ERα) and HER2 status, pre-existing CIN level in cancer cells, and the CIN induced by the treatments. ERα+/HER2− cells with intermediate CIN were sensitive to treatment with taxanes (DOC) and anthracyclines (DOX), while ERα−/HER2−, ERα+/HER2+, and ERα-/HER2+ cells with intermediate CIN were resistant to these treatments. CONCLUSIONS: A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes. |
format | Online Article Text |
id | pubmed-7721098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Compuscript |
record_format | MEDLINE/PubMed |
spelling | pubmed-77210982020-12-08 Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines Vargas-Rondón, Natalia Pérez-Mora, Erika Villegas, Victoria E. Rondón-Lagos, Milena Cancer Biol Med Original Article OBJECTIVE: Chromosomal instability (CIN) is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes, frequently observed in cancer cell populations and is associated with poor prognosis, metastasis, and therapeutic resistance. Breast cancer (BC) is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens. However, paradoxical associations between extreme CIN and improved outcome have been observed. METHODS: This study aimed to 1) evaluate CIN levels and clonal heterogeneity (CH) in MCF7, ZR-751, MDA-MB468, BT474, and KPL4 BC cells treated with low doses of tamoxifen (TAM), docetaxel (DOC), doxorubicin (DOX), Herceptin (HT), and combined treatments (TAM/DOC, TAM/DOX, TAM/HT, HT/DOC, and HT/DOX) by using fluorescence in situ hybridization (FISH), and 2) examine the association with response to treatments by comparing FISH results with cell proliferation. RESULTS: Intermediate CIN was linked to drug sensitivity according to three characteristics: estrogen receptor α (ERα) and HER2 status, pre-existing CIN level in cancer cells, and the CIN induced by the treatments. ERα+/HER2− cells with intermediate CIN were sensitive to treatment with taxanes (DOC) and anthracyclines (DOX), while ERα−/HER2−, ERα+/HER2+, and ERα-/HER2+ cells with intermediate CIN were resistant to these treatments. CONCLUSIONS: A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes. Compuscript 2020-11-15 2020-12-15 /pmc/articles/PMC7721098/ /pubmed/33299647 http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0028 Text en Copyright: © 2020, Cancer Biology & Medicine https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY) 4.0 (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Original Article Vargas-Rondón, Natalia Pérez-Mora, Erika Villegas, Victoria E. Rondón-Lagos, Milena Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title | Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title_full | Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title_fullStr | Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title_full_unstemmed | Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title_short | Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
title_sort | role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721098/ https://www.ncbi.nlm.nih.gov/pubmed/33299647 http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0028 |
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