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| Content Provider | PubMed Central |
|---|---|
| Author | Sundelin, Jeanna Perman Marcus, Ståhlman Lundqvist, Annika Levin, Max Parini, Paolo Johansson, Martin E. Jan, Borén |
| Editor | Chai, Karl X. |
| Copyright Year | 2012 |
| Abstract | Clear-cell renal cell carcinoma (RCC) is, in most cases, caused by loss of function of the tumor suppressor gene von Hippel–Lindau, resulting in constitutive activation of hypoxia-inducible factor (HIF)-1α and expression of hypoxia-induced genes in normoxic conditions. Clear-cell RCC cells are characterized histologically by accumulation of cholesterol, mainly in its ester form. The origin of the increased cholesterol remains unclear, but it is likely explained by an HIF-1α-driven imbalance between cholesterol uptake and excretion. Here, we showed that expression of the very low-density lipoprotein receptor (VLDL-R) was significantly increased in clear-cell RCC human biopsies compared with normal kidney tissue. Partial knockdown of HIF-1α in clear-cell RCC cells significantly reduced the VLDL-R expression, and knockdown of either HIF-1α or VLDL-R reduced the increased lipid accumulation observed in these cells. We also showed increased uptake of fluorescently labeled lipoproteins in clear-cell RCC cells, which was significantly reduced by knockdown of HIF-1α or VLDL-R. Taken together, our results support the concept that the pathological increase of HIF-1α in clear-cell RCC cells upregulates VLDL-R, which mediates increased uptake and accumulation of lipids. These results explain the morphological characteristics of clear-cell RCC, and open up novel possibilities for detection and treatment of clear-cell RCC. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0048694 |
| Starting Page | 48694 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 11 |
| Volume Number | 7 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2012-11-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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