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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 17, 2011 |
| Title |
Differentially expressed genes between oncogene-introduced wild-type and Atf4-/- cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
During oncogenic transformation, cells acquire genetic mutations that override the normal mechanisms regulating cellular proliferation. Excessive expression of activating transcription factor 4 (ATF4) is often observed in mammalian malignant tumors. However, little is known about the role of ATF4 in the malignant transformation of normal cells. Here, we show that ATF4 promotes oncogene-induced malignant transformation of murine fibroblasts by suppressing the expression of cellular senescence-associated genes. Ectopic expression of oncogenes, H-rasV12 and simian virus 40 large T-antigen, elicited malignant transformation of embryonic fibroblasts from wild-type mice, but not from Atf4-null (Atf4-/-) mice. The oncogenic stresses induced the expression of both Atf4 and cyclin-dependent kinase inhibitor 2a (Cdkn2a), in wild-type cells. Elevated levels of ATF4 successively suppressed the expression of cdkn2a encoding the cellular senescence-associated proteins, p16INK4a and p19ARF, thereby promoting oncogenic transformation. Conversely, the loss of ATF4 caused cellular senescence resulting from the consistent expression of p16INK4a and p19ARF. These findings reveal a novel function of ATF4: that of promoting oncogenic transformation by suppressing cellular senescence.
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| Overall design |
Total 2 samples were derived from [1] H-Ras and SV40T expressing vector-transfected wild-type mouse embryonic fibroblasts (MEFs) and [2] H-Ras and SV40T expressing vector-transfected Atf4-/- MEFs
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| Contributor(s) |
Koyanagi S, Horiguchi M, Okamoto A, Suzuki S, Matsunaga N, Ohdo S |
| Citation(s) |
22102693 |
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| Submission date |
Aug 16, 2011 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Satoru Koyanagi |
| E-mail(s) |
[email protected]
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| Organization name |
Kyushu University
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| Department |
Pharmaceutics
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| Street address |
3-1-1 Maidashi, Higashi-ku
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| City |
Fukuoka |
| State/province |
Fukuoka |
| ZIP/Postal code |
812-8582 |
| Country |
Japan |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA145731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31405_RAW.tar |
17.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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