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| Status |
Public on Aug 21, 2010 |
| Title |
Expression data from Control and Six1 expressing MCF7 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases Transforming Growth Factor-beta (TGF-beta) signaling in mammary carcinoma cells and induces an epithelial to mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-beta signaling. TGF-beta signaling and EMT have been implicated in metastatic dissemination of carcinoma. Using spontaneous and experimental metastasis mouse models, we demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-beta signaling. Importantly, in human breast cancers Six1 significantly correlates with nuclear Smad3, and thus increased TGF-beta signaling. Further, breast cancer patients whose tumors overexpress Six1 have a shortened time to relapse and metastasis, and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlates with adverse outcomes in numerous other cancers, including brain, cervical, prostate, colon, kidney, and liver, amongst others. Our findings argue that Six1, acting through TGF-beta signaling and EMT, is a powerful and global promoter of cancer metastasis.
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| Overall design |
This study has two parts: the first part compared three Control and three Six1 expressing MCF7 clones. Total RNA was isolated from each clone on two separate occassions and hybridized to Affymetrix arrays. The second part compared MCF7-control and Six1 expressing cell lines expressing either GFP control or TbetaRIIDN. Total RNA was isolated from each cell line on two separate occassions and hybridized to Affymetrix arrays
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| Contributor(s) |
Ford HL, Micalizzi DS |
| Citation(s) |
19726885, 22466647 |
| Submission date |
Aug 16, 2010 |
| Last update date |
Mar 12, 2017 |
| Contact name |
Heide Ford |
| E-mail(s) |
heide.ford@ucdenver.edu
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| Organization name |
University of Colorado at Denver
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| Department |
OB/Gyn
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| Street address |
12800 E 19th Ave RC1 North, Room 5102
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| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL3921 |
[HT_HG-U133A] Affymetrix HT Human Genome U133A Array |
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| Samples (20)
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| GSM580380 |
MCF7-Control clone 1 biological rep 1 |
| GSM580381 |
MCF7-Control clone 1 biological rep 2 |
| GSM580382 |
MCF7-Control clone 2 biological rep 1 |
| GSM580383 |
MCF7-Control clone 2 biological rep 2 |
| GSM580384 |
MCF7-Control clone 3 biological rep 1 |
| GSM580385 |
MCF7-Control clone 3 biological rep 2 |
| GSM580386 |
MCF7-Six1 clone 1 biological rep 1 |
| GSM580387 |
MCF7-Six1 clone 1 biological rep 2 |
| GSM580388 |
MCF7-Six1 clone 2 biological rep 1 |
| GSM580389 |
MCF7-Six1 clone 2 biological rep 2 |
| GSM580390 |
MCF7-Six1 clone 3 biological rep 1 |
| GSM580391 |
MCF7-Six1 clone 3 biological rep 2 |
| GSM580415 |
MCF7-Control-GFP cell line biological rep 1 |
| GSM580416 |
MCF7-Control-GFP cell line biological rep 2 |
| GSM580417 |
MCF7-Control-TbetaRIIDN cell line biological rep 1 |
| GSM580418 |
MCF7-Control-TbetaRIIDN cell line biological rep 2 |
| GSM580419 |
MCF7-Six1-GFP cell line biological rep 1 |
| GSM580420 |
MCF7-Six1-GFP cell line biological rep 2 |
| GSM580421 |
MCF7-Six1-TbetaRIIDN cell line biological rep 1 |
| GSM580422 |
MCF7-Six1-TbetaRIIDN cell line biological rep 2 |
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| Relations |
| BioProject |
PRJNA130855 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23655_RAW.tar |
70.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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