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| Status |
Public on Dec 01, 2011 |
| Title |
Transcriptional profiling of liver tissue from mice with wild-type, N750F mutant or exon 19 deleted RB1, after treatment with diethylnitrosamine. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The LXCXE peptide motif facilitates interaction between the RB tumor suppressor and a large number of cellular proteins that are expected to impinge on diverse biological processes. In vitro and in vivo analyses demonstrated that LXCXE-binding function is dispensable for RB promoter association and control of basal gene expression. Dependence on this function of RB is unmasked after DNA damage, wherein LXCXE-binding is essential for exerting control over E2F3 and suppressing cell cycle progression in the presence of genotoxic stress. Gene expression profiling revealed that the transcriptional program coordinated by this specific aspect of RB is associated with progression of human hepatocellular carcinoma and poor disease outcome. Consistent with these findings, biological challenge revealed a requirement for LXCXE-binding in suppression of genotoxin-initiated hepatocellular carcinoma in vivo. Together, these studies establish an essential role of the LXCXE-binding motif for RB-mediated transcriptional control, response to genotoxic insult, and tumor suppression.
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| Overall design |
Mice transgenic for Cre-recombinase under the albumin promoter contain indicated combinations of loxP sites flanking exon 19 of Rb1 (f), N750F mutation (NF) or wild-type (plus) genotypes. For gene expression microarray analysis, mice were aged to 14 days and treated for 24 hours with diethylnitrosamine (DEN) or saline as an “untreated” control. Liver tissue was obtained from DEN treated livers and compared to normal liver tissue of saline treated littermates.
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| Contributor(s) |
Bourgo RJ, Knudsen ES, Ertel AA |
| Citation(s) |
21855804 |
| Submission date |
Aug 03, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Adam Ertel |
| Organization name |
Thomas Jefferson University
|
| Department |
Cancer Biology
|
| Lab |
BLSB 1009
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| Street address |
233 S 10TH ST
|
| City |
PHILADELPHIA |
| State/province |
PA |
| ZIP/Postal code |
19107 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA144791 |
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