 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 28, 2017 |
| Title |
Global gene expression changes during human Angiomyolipoma xenograft propagation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Angiomyolipoma (AML), the most common benign renal tumor, can result in severe morbidity from hemorrhage and renal failure. While mTORC1 activation is involved in its growth, mTORC1 inhibitors fail to eradicate AML, highlighting the need for new therapies. Moreover, the identity of the AML cell of origin is obscure. AML research, however, is hampered by the lack of in-vivo models. Here, we establish a human AML-xenograft (Xn) model in mice, recapitulating AML at the histological and molecular levels. Microarray analysis demonstrated tumor growth in-vivo to involve robust PPARG-pathway activation. Similarly, immunostaining revealed strong PPARG expression in human AML specimens. Accordingly, we demonstrate that while PPARG agonism accelerates AML growth, PPARG antagonism is inhibitory, strongly suppressing AML proliferation and tumor-initiating capacity, via an anti-TGFb mechanism. Finally, we show striking similarity between AML cell lines and multipotent mesenchymal stromal cells (MSCs) in terms of antigen and gene expression and differentiation potential. Altogether, we establishment the first in-vivo human AML model, provide evidence that AML may originate in a PPARG-activated renal MSC lineage that is skewed towards adipocytes and smooth muscle and away from osteoblasts, and uncover PPARG as a regulator of AML growth, which could serve as an attractive therapeutic target.
|
| |
|
| Overall design |
In order to investigate the genetic changes accompanying AML Xn propagation, we compared the cell of origin of the Xn (i.e. the UMB cell line, derived from the AML of a human TSC patient), a first-generation Xn (T1), a fourth-generation Xn (T4) and primary human bone marrow-derived multipotent marrow stromal cells (MSCs), hypothesized to represent the AML cell of origin. The study was aimed at analyzing mainly the changes in gene expression accompanying the propagation of the AML Xn, by comparing T4- to T1-Xn. In addition, we were interested in studying the changes from MSCs (representing the presumptive cell of origin of the tumor) to UMB (representing a transformed equivalent of the former).
|
| |
|
| Contributor(s) |
Pleniceanu O, Shukrun R, Omer D, Vax E, Dziedzic K, Mark-Daniei M, Pri-Chen S, Varda-Bloom N, Nagler A, Harari-Steinberg O, Arbiser JL, Dekel B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jan 26, 2017 |
| Last update date |
Oct 25, 2022 |
| Contact name |
jasmine Jacob |
| E-mail(s) |
j-jacob@sheba.health.gov.il
|
| Phone |
0523790500
|
| Organization name |
Sheba Medical Center at Tel HaShomer
|
| Street address |
haChevel 33
|
| City |
Shoham |
| State/province |
-Select- |
| ZIP/Postal code |
60850 |
| Country |
Israel |
| |
|
| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA368960 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94114_RAW.tar |
6.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...