CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells
Background : CyclinD1 is an essential sensor and activator of cell cycle initiation and progression; overexpression of cyclinD1 is linked to various human cancers, including breast cancer. The elevated cyclinD1 in some types of cancers is believed to be associated with tumor progression and response...
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Wolters Kluwer Medknow Publications
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doaj-af519b54c47f4c929a02e69e4bd4d8492020-11-24T23:44:12ZengWolters Kluwer Medknow PublicationsJournal of Carcinogenesis1477-31632012-01-01111121210.4103/1477-3163.100401CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cellsYuan SunDianzhong LuoD Joshua LiaoBackground : CyclinD1 is an essential sensor and activator of cell cycle initiation and progression; overexpression of cyclinD1 is linked to various human cancers, including breast cancer. The elevated cyclinD1 in some types of cancers is believed to be associated with tumor progression and response to systemic treatments. Aims : In this study, we anticipate to address the questions in human breast cancer; the function of cyclinD1 in mediating chemoresponses; and the signaling pathway cooperating with cyclinD1 to interfere with the drug functions. Materials and Methods: Using the cell clones, concurrent ectopic expression of the wild-type or K112E-mutated human cyclinD1 protein in the MCF7 and MDA-MB231 (MB231) breast cancer cells to study the function of cyclinD1 in responses to the chemotherapeutic treatments. Three drugs, cisplatin (CDDP), 5-fluorouracil (5-FU), and Gemzar were used in this study; the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle and cell death analysis, clonogenic survival assay, acridine orange (AO)/ethidium bromide (EB) staining, and Western blot assay were conducted to evaluate the drugs′ effects in the cell clones. Results: The cell clones expressing the D1 protein in MCF7 and MB231 cells result in distinct effects on the responses to chemotherapeutic treatments. Particularly with Gemzar, ectopic expression of cyclinD1 protein in MCF7 cells results in a potentiated effect, which is CDK4 kinase activity dependent, whereas in MB231 cells, an opposite effect was observed. Moreover, our results suggested that the distinct chemosensitivities among those cell clones were not resulted from accelerated cell cycle, cell proliferation driven by the cyclinD1CDK4/6-Rb-E2F signaling chain, rather, they were results of the cell cycle-independent functions led by cyclinD1 alone or in complex with CDK4. Conclusions: Our results suggest that the functions of cyclinD1 protein in modulating chemoresponses in the MCF7 and MB231 cells are independent to its function as cell cycle initiator through activation of CDK4/6. Furthermore, the signals modulated by cyclinD1 upon treatment are determined by the drug and the cellular network.http://www.carcinogenesis.com/article.asp?issn=1477-3163;year=2012;volume=11;issue=1;spage=12;epage=12;aulast=SunBreast cancerCDK4/6 kinasechemosensitivitycyclinD1NF-kBTGF-β |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan Sun Dianzhong Luo D Joshua Liao |
spellingShingle |
Yuan Sun Dianzhong Luo D Joshua Liao CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells Journal of Carcinogenesis Breast cancer CDK4/6 kinase chemosensitivity cyclinD1 NF-kB TGF-β |
author_facet |
Yuan Sun Dianzhong Luo D Joshua Liao |
author_sort |
Yuan Sun |
title |
CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells |
title_short |
CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells |
title_full |
CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells |
title_fullStr |
CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells |
title_full_unstemmed |
CyclinD1 protein plays different roles in modulating chemoresponses in MCF7 and MDA-MB231 cells |
title_sort |
cyclind1 protein plays different roles in modulating chemoresponses in mcf7 and mda-mb231 cells |
publisher |
Wolters Kluwer Medknow Publications |
series |
Journal of Carcinogenesis |
issn |
1477-3163 |
publishDate |
2012-01-01 |
description |
Background : CyclinD1 is an essential sensor and activator of cell cycle initiation and progression; overexpression of cyclinD1 is linked to various human cancers, including breast cancer. The elevated cyclinD1 in some types of cancers is believed to be associated with tumor progression and response to systemic treatments. Aims : In this study, we anticipate to address the questions in human breast cancer; the function of cyclinD1 in mediating chemoresponses; and the signaling pathway cooperating with cyclinD1 to interfere with the drug functions. Materials and Methods: Using the cell clones, concurrent ectopic expression of the wild-type or K112E-mutated human cyclinD1 protein in the MCF7 and MDA-MB231 (MB231) breast cancer cells to study the function of cyclinD1 in responses to the chemotherapeutic treatments. Three drugs, cisplatin (CDDP), 5-fluorouracil (5-FU), and Gemzar were used in this study; the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle and cell death analysis, clonogenic survival assay, acridine orange (AO)/ethidium bromide (EB) staining, and Western blot assay were conducted to evaluate the drugs′ effects in the cell clones. Results: The cell clones expressing the D1 protein in MCF7 and MB231 cells result in distinct effects on the responses to chemotherapeutic treatments. Particularly with Gemzar, ectopic expression of cyclinD1 protein in MCF7 cells results in a potentiated effect, which is CDK4 kinase activity dependent, whereas in MB231 cells, an opposite effect was observed. Moreover, our results suggested that the distinct chemosensitivities among those cell clones were not resulted from accelerated cell cycle, cell proliferation driven by the cyclinD1CDK4/6-Rb-E2F signaling chain, rather, they were results of the cell cycle-independent functions led by cyclinD1 alone or in complex with CDK4. Conclusions: Our results suggest that the functions of cyclinD1 protein in modulating chemoresponses in the MCF7 and MB231 cells are independent to its function as cell cycle initiator through activation of CDK4/6. Furthermore, the signals modulated by cyclinD1 upon treatment are determined by the drug and the cellular network. |
topic |
Breast cancer CDK4/6 kinase chemosensitivity cyclinD1 NF-kB TGF-β |
url |
http://www.carcinogenesis.com/article.asp?issn=1477-3163;year=2012;volume=11;issue=1;spage=12;epage=12;aulast=Sun |
work_keys_str_mv |
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