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| Status |
Public on Feb 14, 2017 |
| Title |
MMS induced expression changes (Mouse) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.
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| Overall design |
Gene expression of four biological replicates of primary C57BL6/J mouse embryonic fibroblasts. Cell were plated and medium was exchanged 24 hours later for media either without (Ctrl) or with MMS (MMS at 40 µg/mL) treatment. RNA was harvested either 0, 1, 8, 24 or 72 hours following initiation of MMS exposure.
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| Contributor(s) |
Zanotto-Filho A, Dashnamoorthy R, Masamsetti P, Loranc E, Rajamanickam S, Chavez-Santoscoy AV, Tonapi SS, Reddick RL, Suresh U, Chen Y, Bishop AJ |
| Citation(s) |
27100653 |
| |
| Submission date |
May 19, 2014 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Yidong Chen |
| E-mail(s) |
[email protected]
|
| Phone |
2105629163
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| Organization name |
UT Health Science Center at San Antonio
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| Department |
Population Health Sciences
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| Street address |
8403 Floyd Curl Drive, MSC 7784
|
| City |
San Antonio |
| State/province |
Texas |
| ZIP/Postal code |
78229 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (35)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA248123 |
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