Proteome-wide profiling of the MCF10AT breast cancer progression model.
Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-06-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2882958?pdf=render |
| _version_ | 1818336443834040320 |
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| author | Lee Yee Choong Simin Lim Poh Kuan Chong Chow Yin Wong Nilesh Shah Yoon Pin Lim |
| author_facet | Lee Yee Choong Simin Lim Poh Kuan Chong Chow Yin Wong Nilesh Shah Yoon Pin Lim |
| author_sort | Lee Yee Choong |
| collection | DOAJ |
| description | Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer.We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the "Warburg effect"). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions.The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre-neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy. |
| first_indexed | 2024-12-13T14:39:25Z |
| format | Article |
| id | doaj.art-e20e1281832a4bd68bf76cfc1a7f32e8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T14:39:25Z |
| publishDate | 2010-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e20e1281832a4bd68bf76cfc1a7f32e82022-12-21T23:41:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-06-0156e1103010.1371/journal.pone.0011030Proteome-wide profiling of the MCF10AT breast cancer progression model.Lee Yee ChoongSimin LimPoh Kuan ChongChow Yin WongNilesh ShahYoon Pin LimMapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer.We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the "Warburg effect"). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions.The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre-neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy.http://europepmc.org/articles/PMC2882958?pdf=render |
| spellingShingle | Lee Yee Choong Simin Lim Poh Kuan Chong Chow Yin Wong Nilesh Shah Yoon Pin Lim Proteome-wide profiling of the MCF10AT breast cancer progression model. PLoS ONE |
| title | Proteome-wide profiling of the MCF10AT breast cancer progression model. |
| title_full | Proteome-wide profiling of the MCF10AT breast cancer progression model. |
| title_fullStr | Proteome-wide profiling of the MCF10AT breast cancer progression model. |
| title_full_unstemmed | Proteome-wide profiling of the MCF10AT breast cancer progression model. |
| title_short | Proteome-wide profiling of the MCF10AT breast cancer progression model. |
| title_sort | proteome wide profiling of the mcf10at breast cancer progression model |
| url | http://europepmc.org/articles/PMC2882958?pdf=render |
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