Hepatitis B virus X protein upregulates HSP90alpha expression via activation of c-Myc in human hepatocarcinoma cell line, HepG2

<p>Abstract</p> <p>Background</p> <p>The Hepatitis B Virus X protein (HBx) plays a major role in hepatocellular carcinoma (HCC) development, however, its contribution to tumor invasion and metastasis has not been established so far. Heat shock protein 90 alpha (HSP90alpha) isoform is an ATP-dependent molecular chaperone that maintains the active conformation of client oncoproteins in cancer cells, which is abundantly expressed in HCC, especially in hepatitis B virus (HBV)-related tumors, might be involved in tumor progression.</p> <p>Methods</p> <p>The levels of HSP90alpha, extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2) and c-Myc in HBx-transfected HepG2 cells were determined by western blots analysis. The endogenous ERKs activity was demonstrated by ELISA assay. The regulation of c-Myc-mediated HSP90 alpha promoter transactivation by HBx was evaluated through electrophoretic mobility shift analysis (EMSA). The c-Myc-mediated HSP90alpha transcription was analysed by promoter assay. The HBx-expressing cells were transfected with specific small interference RNA (siRNA) against c-Myc. The <it>in vitro </it>invasion potentials of cells were evaluated by Transwell cell invasion assay.</p> <p>Results</p> <p>HBx induces HSP90alpha expression at the transcription level. The induction effect of HBx was inhibited after treatment with c-Myc inhibitor, 10058-F4. In addition, the luciferase activity of the HSP90alpha promoter analysis revealed that the HBx is directly involved in the c-Myc-mediated transcriptional activation of HSP90alpha. Furthermore, HBx induces c-Myc expression by activation of Ras/Raf/ERK1/2 cascades, which in turn results in activation of the c-Myc-mediated HSP90alpha promoter and subsequently up-regulation of the HSP90alpha expression. Overexpression of HSP90alpha in HBx-transfected cells enhances tumor cells invasion. siRNA-mediated c-Myc knockdown in HBx-transfected cells significantly suppressed HSP90alpha expression and cells invasion <it>in vitro</it>.</p> <p>Conclusion</p> <p>These results demonstrate the ability of HBx to promote tumor cells invasion by a mechanism involving the up-regulation of HSP90alpha and provide new insights into the mechanism of action of HBx and its involvement in tumor metastasis and recurrence of HCC.</p

Epiglottic masses identified on CT imaging: A case report and review of the broad differential diagnosis

Epiglottic masses may be cystic, granulomatous, infectious, benign or malignant neoplastic, or manifestations of a systemic disease. When large in size, the airway may become obstructed, and when accompanied by suspicious features such as cartilaginous invasion, extension to the pre-epiglottic or para-glottic spaces, or lymphadenopathy, the radiologist must consider malignancy as a primary differential diagnosis. However, when only benign features are identified, the differential diagnosis is broad. We present a 65-year-old female with an incidental 1 cm exophytic, pedunculated, papillomatous lesion on the laryngeal surface of the epiglottis discovered upon endoscopic evaluation for dyspepsia and heartburn. Because of her risk factors for malignancy, CT scan was requested and revealed only benign features. Subsequent excisional biopsy revealed a benign squamous papilloma; however, multiple additional differential considerations were entertained preoperatively