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| Status |
Public on Sep 21, 2012 |
| Title |
EZH2 promotes a bi-lineage identity in basal-like breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a “bi-lineage” differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal progenitor gene expression. GATA3 levels increase upon EZH2 silencing, leading to the observed decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.
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| Overall design |
Total of four treatments (HCC70 cells stably expressing shEZH2, shEED, or EZH2 cDNA, and MDA-MB-468 cells stably expressing shEZH2) were done in duplicates, each with its own control.
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| Contributor(s) |
Granit RZ, Gabai Y, Hadar T, Karamansha Y, Liberman L, Waldhorn I, Gat-Viks I, Regev A, Maly B, Peretz T, Ben-Porath I |
| Citation(s) |
22986524 |
| Submission date |
Mar 29, 2012 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Ittai Ben-Porath |
| E-mail(s) |
roy.granit@mail.huji.ac.il
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| Phone |
97226758150
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| Organization name |
Hebrew University of Jerusalem
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| Department |
Developmental Biology and Cancer Research
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| Lab |
Ittai Ben-Porath
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| Street address |
Faculty of Medicine, Ein kerem
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| City |
Jerusalem |
| ZIP/Postal code |
Jerusalem 91120, Israel |
| Country |
Israel |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (16)
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| GSM906680 |
HCC70 shEZH2, replicate 2 |
| GSM906681 |
MDA-MB-468 shCont, replicate 1 |
| GSM906682 |
MDA-MB-468 shCont, replicate 2 |
| GSM906683 |
MDA-MB-468 shEZH2, replicate 1 |
| GSM906684 |
MDA-MB-468 shEZH2, replicate 2 |
| GSM906685 |
HCC70 shCont, replicate 1b |
| GSM906686 |
HCC70 shCont, replicate 2b |
| GSM906687 |
HCC70 shEED, replicate 1 |
| GSM906688 |
HCC70 shEED, replicate 2 |
| GSM906689 |
HCC70 plKO Puro, replicate 1 |
| GSM906690 |
HCC70 plKO Puro, replicate 2 |
| GSM906691 |
HCC70 fip EZH2, replicate 1 |
| GSM906692 |
HCC70 fip EZH2, replicate 2 |
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| Relations |
| BioProject |
PRJNA157129 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36939_RAW.tar |
64.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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