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| Content Provider | PubMed Central |
|---|---|
| Author | Gordan, John D. Lal, Priti Dondeti, Vijay R. Richard, Letrero Parekh, Krishna N. Oquendo, C. Elisa Greenberg, Roger A. Flaherty, Keith T. Rathmell, W. Kimryn Keith, Brian Simon, M. Celeste Nathanson, Katherine L. |
| Abstract | VHL tumor suppressor loss results in hypoxia inducible factor-alpha (HIF-α) stabilization, and occurs in 70% of sporadic clear cell renal carcinomas (ccRCCs). To determine whether opposing influences of HIF-1α and HIF-2α on c-Myc activity regulate human ccRCC progression, we analyzed VHL genotype and HIF-α expression in 160 primary tumors, which segregated into three groups with distinct molecular characteristics. Interestingly, ccRCCs with intact VHL, as well as pVHL-deficient, HIF-1α/HIF-2α expressing ccRCCs, exhibited enhanced Akt/mTOR and ERK/MAPK signaling. In contrast, pVHL-deficient ccRCCs expressing only HIF-2α displayed elevated c-Myc activity, resulting in enhanced proliferation and resistance to replication stress. These reproducible distinctions in ccRCC behavior delineate HIF-α effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies. |
| Related Links | http://dx.doi.org/10.1016/j.ccr.2008.10.016 |
| Ending Page | 446 |
| Page Count | 12 |
| Starting Page | 435 |
| File Format | |
| ISSN | 15356108 |
| Journal | Cancer cell |
| Issue Number | 6 |
| Volume Number | 14 |
| Language | English |
| Publisher Date | 2008-12-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Cancer Research Oncology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Cancer Research Oncology |
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