Von Hippel-Lindau gene

Lieubeau-TeiUet, B., Rak, J., Jothy, S., Iliopoulos, O., Kaelin, W. and Kerbel, R. S. (1998). von Hippel-Lindau gene-mediated growth suppression and induction of differentiation in renal cell carcinoma cells grown as multicellular tumor spheroids. Cancer Res. 58,4957-4962. 

Vortmeyer AO, Huang SC, Koch CA, et al. Somatic von Hippel-Lindau gene mutations detected in sporadic endolymphatic sac tumors. Cancer Res. 2000 60 5963-5965. 

Lin F, Shi J, Liu Li, et al. Immunohistochemical detection of the von Hippel-Lindau gene product (pVLiL) in human tissues and tumors A useful marker for metastatic renal cell carcinoma and clear cell carcinoma of the ovary and uterus. Am J Clin Pathol. 2008 129 592-605. 

Datta K, Sundberg C, Karumanchi SA, Mukhopadhyay D. The 104-123 amino acid sequence of the beta-domain of von Hippel-Lindau gene product is sufficient to inhibit renal tumor growth and invasion. Cancer Res 2001 61 1768-1775... 

Datta K, Nambudripad R, Pal S, Zhou M, Cohen HT, Mukhopadhyay D. Inhibition of insulin-like growth factor-I-mediated cell signaling by the von Hippel-Lindau gene product in renal cancer. J Biol Chem 2000 275 20700-20706. 

Zia MK, Rmali KA, Watkins G, Mansel RE, Jiang WG. The expression of the von Hippel-Lindau gene product and its impact on invasiveness of human breast cancer cells. Int J Mol Med 2007 20 605-611. 

Schoenfeld A, Davidowitz EJ, Burk RD. A second major native von Hippel-Lindau gene product, initiated fi om an internal translation start site, functions as a tumor suppressor. Proc Natl Acad Sci USA 1998 95 8817-8822. 

Corless CL, Kibel AS, Iliopoulos O, Kaelin WG, Jr. Itnmunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum Pathol 1997 28 459-464. 

Iliopoulos O, Kibel A, Gray S, Kaelin Jr, WG. Tumour suppression by the human von Hippel-Lindau gene product. Nat Med 1995 1 822-826. 

Pause, A., et al.. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci USA, 1997, 94(6), 2156-61. 

Latif, F. et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260, 1317-20. 

Recent studies have demonstrated that overexpression of HDACl represses the tumor suppressors, p53 and von Hippel-Lindau (VHL), but induces the hypoxia-responsive genes, hypoxia inducible factor alpha (HIF-la) and vascular endothelial growth factor (VEGF) and increases angiogenesis. Conversely, HDAC inhibitors derepress the tumor suppressors, p53 and VHL, and repress HIF-la and VEGF [68, 69]. 

According to the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC), RCC can be histopafhologically classified into the most prominent clear cell type, which is associated with the occurrence of highly specific deletion of chromosome 3p and mutation of the von Hippel Lindau VHL) gene as well as the chromophobe, papillary/chromophil or collecting duct types (Kovacs, 1999). 

Recent comparison of gene expression profiles of von Hippel-lindau-i- versus von Hippel-lindau-ceU lines obtained from the clear cell RCC subtype identified proteins that might serve as candidate molecular markers. Inactivation of VHL is a hallmark in most sporadic clear cell RCC and it occurs early in renal carcinogenesis (Skates and Iliopoulus., 2004 Latifet al, 1993). Furthermore, the profile of secreted proteins could be directly AQ4 determined by analyzing comparatively the genomic and proteomic patterns of these cell lines as well as their conditioned tissue culture supernatants (Ferguson et al, 2004). A combination of cDNA microarray and proteome analyses appears reasonable since not every difference at the transcriptome level will translate into differences at the protein level, whereas posttranscriptional/posttranslational modifications were not detectable by tran-scriptomics. 

Carlo H, Schwarz K, Jorch N, Kyank U, Petrides PE, Schneider DT, Uhle R, Debatin KM, Kohne E. Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis. Haematologica 2005 90 19-24. 

Krieg M, Haas R, Branch H, Acker T, Flamme I, Plate KH. Up-regulation of hypoxia-inducible factors HIE-1 alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 2000 19 5435-5443. 

Von Hippel-Lindau disease is inherited on an autosomal dominant gene that may show marked expressive variability of cancer phenotype in certain patients and families. A patient with a strongly positive family history of this disease, at age 28, underwent craniotomy with removal of a cystic cerebellar hemangioblastoma. At age 48 he developed syringomyelia of the spinal cord, became quadriplegic, and had a progressive downhill course. At autopsy, hemangioblastomas... 

About 5% to 10% of GI neuroendocrine tumors are associated with a hereditary disease. The inherited syndromes and their associated genes include multiple endocrine neoplasia type I MENl gene), neurofibromatosis type 1 NFl gene), von Hippel-Lindau disease VHL gene), and the tuberous sclerosis complex TSCl or TSC2 gene).406... 

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