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| Status |
Public on Mar 31, 2011 |
| Title |
Expression data from BJ-hTERT cells expressing vector, Cyclin E, c-Myc or coexpression of both |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Chromosomal instability in early cancer stages is caused by stress on DNA replication. The molecular basis for replication perturbation in this context is currently unknown. We studied the replication dynamics in cells in which a regulator of S-phase entry and cell proliferation, the Rb-E2F pathway, is aberrantly activated. Aberrant activation of this pathway by HPV-16 E6/E7 or cyclin E oncogenes, significantly decreased the cellular nucleotide levels in the newly transformed cells. Exogenously supplied nucleosides rescued the replication stress and DNA damage, and dramatically decreased oncogene-induced transformation. Increased transcription of nucleotide biosynthesis genes, mediated by expressing the transcription factor c-Myc, increased the nucleotide pool and also rescued the replication-induced DNA damage. Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability.
In order to understand the molecular basis for the low nucleotide pool in cells enforced to proliferate by oncogene expression, we performed unbiased whole transcriptome analysis of BJ cells in comparison to BJ cells expressing cyclin E, c-Myc and cells co-expressing both oncogenes. Our results suggest that Rb-E2F aberrant activation enforces cell proliferation but fails to activate the nucleotide biosynthesis pathway leading to insufficient pool of nucleotides required for normal replication.
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| Overall design |
We analyzed two sets of BJ cells infected with empty pBabe, Cyclin E, c-Myc or coexpression of Cyclin E and c-Myc
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| Contributor(s) |
Kerem B, Bester A |
| Citation(s) |
21529715 |
| Submission date |
Mar 30, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Batsheva kerem |
| E-mail(s) |
kerem@cc.huji.ac.il
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| Organization name |
The Hebrew University of Jerusalem
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| Department |
Department of Genetics
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| Street address |
Edmond Safra Campus
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| City |
Jerusalem |
| ZIP/Postal code |
91904 |
| 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 (7)
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| Relations |
| BioProject |
PRJNA139271 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28266_RAW.tar |
29.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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