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The aim of the present study was to investigate the clinical characteristics and management of primary renal sinus tumors. We retrospectively analyzed three cases of primary renal sinus tumors. The first patient was a 33-year-old man who presented with right flank pain for 6 months. Based on the imaging results, the patient was diagnosed with renal sinus tumor. The second case was a 34-year-old woman who presented with sudden lumbago in the right flank for 3 days. The imaging results confirmed the diagnosis of right renal angiomyolipoma. The third case was a 55-year-old woman with flank pain, which had persisted for 1 year. The imaging tests revealed lipoma of the left renal sinus. All three cases underwent surgical procedures. The first case was diagnosed with benign angioleiomyoma following pathological analysis. During surgery, the tumor was ablated and the kidney was spared. The second case was scheduled for tumor enucleating, but a nephrectomy was performed due to serious hemorrhaging and a damaged renal pelvis. Pathological analysis identified angiomyolipoma. The third case was scheduled for lipoma enucleating; however, nephrectomy was performed as the tumor encapsulated the renal vascular pedicle. Pathological analysis revealed lipoma. In the three cases, no relapse over 3 years, 10 months and 4 years of follow-up, respectively, was observed. In addition, this review examined previous literature and concluded that the occurrence of tumors in the renal sinus is rare and the majority of such tumors are benign. Furthermore, cases are easily misdiagnosed as renal pelvic tumors. Computed tomography, magnetic resonance imaging and intravenous urography are the best imaging examination methods for differential diagnosis. In conclusion, surgery is the usual approach for the treatment of renal sinus tumors and radical nephrectomy should be performed for malignant tumors. [ABSTRACT FROM AUTHOR]

Functional inactivation of the von Hippel-Lindau (VHL) tumor suppressor protein is linked to the development of several forms of cancer as well as oncogenic progression like sporadic renal clear-cell carcinomas (RCC). Despite the critical role played by VHL in destruction of hypoxia-inducible factor α (HIFα) via ubiquitin-mediated proteolysis, very little is known about the post-translational modification which regulates VHL activity. Our previous study showed that the SUMO E3 ligase PIASy interacts with VHL and induces VHL SUMOylation on lysine residue 171 (Cai et al, PLoS ONE, 2010, 5(3):e9720). Here we further report that VHL also undergoes ubiquitylation on both lysine residues 171 and 196, which is blocked by PIASy. Moreover, using a VHL-SUMO1 or ubiquitin fusion protein, we found that ubiquitylated VHL is localized predominantly in the cytoplasm, while SUMOylated VHL results in increased VHL protein stability and nuclear redistribution. Interestingly, substitution of lysine 171 and 196 to arginine of VHL abrogates its inhibitory function on the transcriptional activity of HIFα, and tube formation in vitro. This demonstrates that post-translational modifications like ubiquitylation and SUMOylation contributes to VHL protein stability and nucleocytoplasmic shuttling, and that the overall function of VHL in tumor suppression may require a precise and dynamically regulated process which involves protein modification. [ABSTRACT FROM AUTHOR]

The hypoxic microenvironment contributes to embryonic development and tumor progression through stabilization of the potent transcriptional factor HIFα. In normoxia, the tumor suppressor protein VHL acts as an E3 ubiquitin ligase to target HIFα for proteolytic destruction. Increasing evidence shows that VHL is a multifunctional adaptor involved in inhibition of HIFα-dependent and independent cellular processes. However, the molecular effect of hypoxic stress on VHL functions remains elusive. Here we report that PIASy, a SUMO E3 ligase upregulated in hypoxia, interacts with VHL and induces VHL SUMOylation on lysine residue 171. Moreover, PIASy-mediated SUMO1 modification induces VHL oligomerization and abrogates its inhibitory function on tumor cell growth, migration and clonogenicity. Knockdown of PIASy by small interfering RNA leads to reduction of VHL oligomerization and increases HIF1α degradation. These findings reveal a unique molecular strategy for inactivation of VHL under hypoxic stress. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV; or human herpesvirus 8 [HHV8]) is implicated in the pathogenesis of many human malignancies including Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). KSHV infection displays two alternative life cycles, referred to as the latent and lytic or productive cycle. Previously, we have reported that the replication and transcription activator (RTA), a major lytic cycle transactivator, contributes to the development of KSHV latency by inducing latency-associated nuclear antigen (LANA) expression during early stages of infection by targeting RBP-Jκ, the master regulator of the Notch signaling pathway. Here, we generated a bacterial artificial chromosome (BAC) KSHV recombinant virus with a deletion of the RBP-Jκ site within the LANA promoter to evaluate the function of the RBP-Jκ cognate site in establishing primary latent infection. The results showed that genetic disruption of the RBP-Jκ binding site within the KSHV LANA promoter led to enhanced expression of the KSHV-encoded immediate early RTA, resulting in an increase in lytic replication during primary infection of human peripheral blood mononuclear cells (PBMCs). This system provides a powerful tool for use in indentifying additional cellular and viral molecules involved in LANA-mediated latency maintenance during the early stages of KSHV infection. [ABSTRACT FROM AUTHOR]