|
| Status |
Public on Nov 30, 2011 |
| Title |
ERG deregulation induces PIM-1 over-expression and aneuploidy in prostate epitheilial cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The ERG gene belongs to the ETS family of transcription factors and has been found involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG,. We found that all the three ERG fusions significantly up-regulate PIM-1 expression in the NIH-3T3 cell line. PIM-1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM-1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM-1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM-1 induction. A significant association between ERG and PIM-1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM-1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM-1 expression. The up-regulation of PIM-1 induced by tERG over-expression significantly modified CyclinB1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after 24hrs of taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM-1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability.
|
| |
|
| Overall design |
NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG together with the empty vector where profiled in triplicate. Quality control using NUSE and RLE plots identified one array as problematic (R540_TMP-ERG_P1) which was removed.
|
| |
|
| Contributor(s) |
Magistroni V, Mologni L, Sanselicio S, Reid JF, Redaelli S, Piazza R, Viltadi M, Bovo G, Strada G, Grasso M, Gariboldi M, Gambacorti-Passerini C |
| Citation(s) |
22140532 |
| |
| Submission date |
Sep 29, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Vera Magistroni |
| E-mail(s) |
vera.magistroni@unimib.it
|
| Phone |
+39-0264488362
|
| Fax |
+39-0264488363
|
| Organization name |
University of Milano-Bicocca
|
| Department |
Clinical Medicine and Prevention
|
| Street address |
via Cadore 48
|
| City |
Monza |
| ZIP/Postal code |
20900 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (11)
|
|
| Relations |
| BioProject |
PRJNA147785 |
Less...
More...