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| Status |
Public on Apr 18, 2004 |
| Title |
Cell-type specific responses to chemotherapeutics in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Recent studies have identified clinical subtypes of breast tumors that arise from different cell types and have different outcomes in response to chemotherapy. Tumors derived from basal epithelium have a poorer prognosis than tumors derived from luminal epithelium. To gain insight into differences underlying this disparity, we treated cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and those derived from luminal epithelium (MCF-7 and ZR-75-1) with two chemotherapeutics commonly used in the treatment of breast cancer. Treatment doses for doxorubicin (DOX) and 5-fluorouracil (5FU) were selected to cause comparable cytotoxicity across all four cell lines. The predominant gene expression in each of the four cell lines was a general stress response, but distinct gene expression patterns were observed depending upon cell type. Both cell types up-regulated DNA damage response genes such as p21waf1, but the response in the luminal cells was much more dramatic and included many p53-regulated genes. Luminal cell lines down-regulated a large number of cell cycle regulators and other genes involved in cellular proliferation, while basal cell lines down-regulated a smaller set of genes, many of which are involved in cellular differentiation. These results were compared to gene expression data from tumor samples collected before and after treatment with DOX or 5FU/mitomycin C. Similarities between the in vitro and in vivo responses validate this model for studying gene expression responses to chemotherapy in these cell types. Understanding cell-type specific responses to chemotherapeutics will help in tailoring treatment to patients based upon tumor characteristics.
Keywords = breast cancer
Keywords = chemotherapy
Keywords = gene expression
Keywords = microarray
Keywords = stress response
Keywords: time-course
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| Contributor(s) |
Troester MA, Hoadley KA, Sørlie T, Herbert B, Shay J, Perou CM |
| Citation(s) |
15205334 |
| Submission date |
Oct 21, 2003 |
| Last update date |
Jul 17, 2015 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
cperou@med.unc.edu
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| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
|
| Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
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| Platforms (1) |
| GPL550 |
UNC compugen oligo array for toxgenomics study |
|
| Samples (75)
|
| GSM11683 |
ME16C, 36h, 0.06mM 5FU |
| GSM11684 |
ZR-75-1, 36h, 3.0mM 5FU |
| GSM11685 |
HME-CC, 36h, 0.01mM 5FU |
| GSM11686 |
HME-CC, 36h, 0.2uM DOX |
| GSM11687 |
MCF-7, 12h, 0.9uM DOX |
| GSM11688 |
HME-CC, 36h, 0.2uM DOX B |
| GSM11689 |
MCF-7, 36h, 0.9uM DOX B |
| GSM11690 |
ZR-75-1, 36h, 0.4uM DOX B |
| GSM11691 |
ME16C, 36h, 0.06mM 5FU B |
| GSM11692 |
ZR-75-1, 12h, 3.0mM 5FU |
| GSM11693 |
MCF-7, 12h, 0.9uM DOX B |
| GSM11694 |
ME16C, 12h, 0.5uM DOX B |
| GSM11695 |
ME16C, 12h, 0.5uM DOX |
| GSM11696 |
ZR-75-1, 36h, 3.0mM 5FU B |
| GSM11697 |
ME16C, 12h, 0.06mM 5FU |
| GSM11698 |
HME-CC, 12h, 0.01mM 5FU B |
| GSM11699 |
HME-CC, 36h, 0.01mM 5FU B |
| GSM11703 |
MCF-7, 12h, 0.3mM 5FU |
| GSM11704 |
MCF-7, 36h, 0.9uM DOX C |
| GSM11705 |
MCF-7, 12h, 0.3mM 5FU B |
| GSM11706 |
ZR-75-1, 12h, sham B |
| GSM11707 |
ME16C, 12h, sham |
| GSM11708 |
HME-CC, 12h, sham |
| GSM11709 |
MCF-7, 12h, sham |
| GSM11710 |
HME-CC, 36h, sham |
| GSM11711 |
ZR-75-1, 36h, sham B |
| GSM11712 |
HME-CC, 36h, sham B |
| GSM11713 |
MCF-7, 36h, 0.3mM 5FU |
| GSM11714 |
ME16C, 12h, 0.06mM 5FU B |
| GSM11715 |
ZR-75-1, 24h, 3.0mM 5FU |
| GSM11716 |
ME16C, 12h, sham B |
| GSM11720 |
MCF-7, 12h, sham B |
| GSM11721 |
ME16C, 36h, sham B |
| GSM11722 |
MCF-7, 24h, 0.3mM 5FU |
| GSM11723 |
ME16C, 24h, 0.06mM 5FU |
| GSM11724 |
ZR-75-1, 24h, 3.0mM 5FU B |
| GSM11725 |
MCF-7, 36h, sham |
| GSM11726 |
MCF-7, 24h, sham |
| GSM11727 |
MCF-7, 24h, 0.9uM DOX |
| GSM11728 |
MCF-7, 36h, 0.3mM 5FU B |
| GSM11729 |
ZR-75-1, 24h, sham B |
| GSM11730 |
MCF-7, 24h, 0.3mM 5FU B |
| GSM11731 |
ZR-75-1, 12h, 0.4uM DOX B |
| GSM11732 |
HME-CC, 12h, 0.2uM DOX |
| GSM11733 |
HME-CC, 24h, sham B |
| GSM11734 |
ME16C, 24h, 0.5uM DOX |
| GSM11735 |
HME-CC, 12h, sham B |
| GSM11746 |
ZR-75-1, 24h, sham |
| GSM11836 |
ZR-75-1, 24h, 0.4uM DOX |
| GSM11837 |
MCF-7, 24h, sham B |
| GSM11838 |
MCF-7, 24h, 0.9uM DOX B |
| GSM11839 |
ZR-75-1, 12h, 0.4uM DOX |
| GSM11840 |
HME-CC, 24h, 0.01mM 5FU |
| GSM11841 |
ZR-75-1, 12h, 3.0mM 5FU B |
| GSM11842 |
HME-CC, 24h, 0.2uM DOX |
| GSM11843 |
ME16C, 36h, 0.5uM DOX |
| GSM11844 |
HME-CC, 12h, 0.2uM DOX B |
| GSM11845 |
ME16C, 24h, 0.06mM 5FU B |
| GSM11846 |
HME-CC, 36h, 0.2uM DOX C |
| GSM11847 |
HME-CC, 24h, 0.01mM 5FU B |
| GSM11849 |
ZR-75-1, 24h, 0.4uM DOX B |
| GSM11850 |
ME16C, 24h, sham B |
| GSM11851 |
ME16C, 24h, sham |
| GSM11852 |
ME16C, 36h, sham |
| GSM11853 |
ZR-75-1, 12h, sham |
| GSM11854 |
ZR-75-1, 36h, sham |
| GSM11860 |
HME-CC, 24h, 0.2uM DOX B |
| GSM11861 |
ME16C, 24h, 0.5uM DOX B |
| GSM11862 |
ME16C, 36h, 0.5uM DOX B |
| GSM11863 |
HME-CC, 24h, sham |
| GSM11864 |
MCF-7, 36h, sham B |
| GSM11901 |
ZR-75-1, 12h, 3.0mM 5FU C |
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| Relations |
| BioProject |
PRJNA87715 |
| Supplementary data files not provided |
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