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| Status |
Public on Feb 13, 2016 |
| Title |
HER2 and EGFR dependent activation of RalA in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Activated HER2 and EGFR stimulate the Ras small GTPases, which in turn primarily activate the MAPK, PI3K-Akt and RalGEF-Ral pathways. While activation of the MAPK and PI3K-Akt pathways downstream of HER2 and EGFR promote mammary tumorigenesis, little is known regarding the role of the RalGEF-Ral pathway. RalGEFs convert the small GTPases RalA and RalB to an active GTP-bound state. Of the two proteins, only activated RalA is transforming, while RalB is more important for cell motility, and hence we investigated the role of RalA in HER2-overexpressing and EGFR-positive breast cancer. We now report that shRNA-mediated knockdown of RalA reduced the in vitro transformed growth and in vivo tumorigenic growth of MDA-MB-231 human breast cancer cells, while knockdown of RalB reduced migration and invasion. Lastly, we demonstrate that expression of activated HER2 increases RalA-GTP levels, and that a number of genes associated with activated RalA are elevated in tumor compared to normal mammary tissue. Taken together, these results suggest a possible role for RalA in mammary tumorigenesis.
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| Overall design |
Four independent cultures of HEK-HT cells stably infected with a retrovirus confirmed to expressed RalAQ72L and four independent cultures of HEK-HT cells stably infected with a control retrovirus
RalA activation expression analysis
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| Contributor(s) |
Issaq SH, Brady DC, Kim MK, Hsu DS, Ribar T, Spector NL, Counter CM |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Dec 03, 2009 |
| Last update date |
Dec 06, 2018 |
| Contact name |
David Hsu |
| E-mail(s) |
hsu00018@dm.duke.edu
|
| Phone |
919-684-1739
|
| Fax |
919-668-4777
|
| Organization name |
Duke University
|
| Department |
Institute for Genome Sciences and Policy
|
| Street address |
Rm 2167 CIEMAS Bldg, 101 Science Dr.
|
| City |
Durham |
| State/province |
NC |
| ZIP/Postal code |
27710 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA120877 |
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