| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
nia Nosé
From the Department of Medical Oncology,* Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; Howard Hughes Medical Institute and the Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; the Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and the Laboratory of Anatomic Pathology,¶ Kyoto University Hospital, Kyoto, Japan
Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an allele-specific manner. The best documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and hence target for destruction, the 
subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type 2C VHL disease), in contrast to classical VHL disease, appear to be normal with respect to HIF regulation. Using a simple method for identifying proteins that are differentially secreted by isogenic cell line pairs, we confirmed that the HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells. In addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression and secretion of clusterin, which does not behave like a HIF target. Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohistochemistry. Therefore, clusterin is a secreted marker for a HIF-independent pVHL function that might be especially important in pheochromocytoma development.
This article has been cited by other articles:
 |
|
 |
|
  O. Chayka, D. Corvetta, M. Dews, A. E. Caccamo, I. Piotrowska, G. Santilli, S. Gibson, N. J. Sebire, N. Himoudi, M. D. Hogarty, et al. Clusterin, a Haploinsufficient Tumor Suppressor Gene in Neuroblastomas J Natl Cancer Inst, May 6, 2009; 101(9): 663 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kawanishi, Y. Matsui, M. Ito, J. Watanabe, T. Takahashi, K. Nishizawa, H. Nishiyama, T. Kamoto, Y. Mikami, Y. Tanaka, et al. Secreted CXCL1 Is a Potential Mediator and Marker of the Tumor Invasion of Bladder Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2579 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsutsumi, H. Kuwabara, T. Arai, Y. Xiao, and J. A. DeCaprio Disruption of the Fbxw8 Gene Results in Pre- and Postnatal Growth Retardation in Mice Mol. Cell. Biol., January 15, 2008; 28(2): 743 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, L. Zhang, X. Zhang, Q. Yan, Y. A. Minamishima, A. F. Olumi, M. Mao, S. Bartz, and W. G. Kaelin Jr. Hypoxia-Inducible Factor Linked to Differential Kidney Cancer Risk Seen with Type 2A and Type 2B VHL Mutations Mol. Cell. Biol., August 1, 2007; 27(15): 5381 - 5392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Fish, C. C. Matouk, E. Yeboah, S. C. Bevan, M. Khan, K. Patil, M. Ohh, and P. A. Marsden Hypoxia-inducible Expression of a Natural cis-Antisense Transcript Inhibits Endothelial Nitric-oxide Synthase J. Biol. Chem., May 25, 2007; 282(21): 15652 - 15666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Pollard, M. El-Bahrawy, R. Poulsom, G. Elia, P. Killick, G. Kelly, T. Hunt, R. Jeffery, P. Seedhar, J. Barwell, et al. Expression of HIF-1{alpha}, HIF-2{alpha} (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4593 - 4598. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
