Prohibitin identified by proteomic analysis of prostate biopsies distinguishes hyperplasia and cancer

Ummanni, Ramesh; Junker, Heike; Zimmermann, Uwe; Venz, Simone; Teller, Steffen; Giebel, J.; Scheffold, Christian; Woenckhaus, Christian; Dombrowski, Frank; Walther, Reinhard

doi:10.1016/j.canlet.2008.02.047

Cited by 78 publications

(62 citation statements)

References 41 publications

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“…Several studies have examined the expression patterns of PHB1 in tumor cell lines and many of these suggest that PHB1 levels are elevated in transformed cells or tumors when compared to their normal cell counterparts (13,15,(29)(30)(31)(32)(33)(34)(35)(36). In the present study, we show that PHB1 levels are significantly elevated in membrane fractions isolated from paclitaxel-resistant sublines compared to normal drug-sensitive cells.…”

Section: Discussionsupporting

confidence: 51%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Paclitaxel has emerged as a front line treatment for aggressive malignancies of the breast, lung, and ovary. Successful therapy of cancer is frequently undermined by the development of paclitaxel resistance. There is a growing need to find other therapeutic targets to facilitate treatment of drug-resistant cancers. Using a proteomics approach, elevated levels of Prohibitin1 (PHB1) and GSTπ were found associated with paclitaxel resistance in discrete subcellular fractions of two drug-resistant sublines relative to their sensitive sublines. Immunofluorescence staining and fractionation studies revealed increased levels of PHB1 on the surface of resistant cell lines. Transiently silencing either PHB1 or GSTπ gene expression using siRNA in the paclitaxel-resistant cancer cell sublines partially sensitized these cells toward paclitaxel. Intriguingly, silencing PHB1 but not GSTπ resulted in activation of the intrinsic apoptosis pathway in response to paclitaxel. Similarly, stably silencing either PHB1 or GSTπ significantly improved paclitaxel sensitivity in A549TR cells both in vitro and in vivo. Our results indicate that PHB1 is a mediator of paclitaxel resistance and that this resistance may depend on the cellular localization of the protein. We suggest PHB1 as a potential target for therapeutic strategies for the treatment of drug-resistant tumors.apoptosis | glutathione-S-transferase Pi | mitochondria | plasma membrane | protein translocation

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Section: Discussionsupporting

confidence: 51%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…However, conflicting results have reported the overexpression of prohibitin in many other cancers, such as uterine, cervix, bladder, and lung cancer (Tsai et al 2006, Wu et al 2007, Guo et al 2012 and even in the same type of cancers , Ummanni et al 2008. Franzoni et al (2009) demonstrated the high expression of prohibitin in PTCs bearing the BRAF V600E mutation but low expression in follicular adenoma.…”

Section: Endocrine-related Cancermentioning

confidence: 99%

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Li¹,

Wang²,

Liu³

et al. 2012

Endocrine-Related Cancer

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The fusion gene encoding the thyroid-specific transcription factor PAX8 and peroxisome proliferator-activated receptor g (PPARg (PPARG)) (designated as the PPFP gene) is oncogenic and implicated in the development of follicular thyroid carcinoma (FTC). The effects of PPFP transfection on the biological characteristics of Nthy-ori 3-1 cells were studied by MTT assay, colony formation, soft-agar colony formation, and scratch wound-healing assays as well as by flow cytometry. Furthermore, the differentially expressed proteins were analyzed on 2-DE maps and identified by MALDI-TOF-MS. Validation of five identified proteins (prohibitin, galectin-1, cytokeratin 8 (CK8), CK19, and HSP27) was determined by western blot analysis. PPFP not only significantly increased the viability, proliferation, and mobility of the Nthy-ori 3-1 cells but also markedly inhibited cellular apoptosis. Twenty-eight differentially expressed proteins were identified, among which 19 proteins were upregulated and nine proteins were downregulated in Nthy-ori 3-1 PPFP (Nthy-ori 3-1 cells transfected with PPFP). The western blot results, which were consistent with the proteome analysis results, showed that prohibitin was downregulated, whereas galectin-1, CK8, CK19, and HSP27 were upregulated in Nthy-ori 3-1 PPFP . Our results suggest that PPFP plays an important role in malignant thyroid transformation. Proteomic analysis of the differentially expressed proteins in PPFP-transfected cells provides important information for further study of the carcinogenic mechanism of PPFP in FTCs.

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“…Protein identification was performed, as described recently (29). Protein spots from Gelcode-stained 2D gels were selected and excised manually using a clean razor blade.…”

Section: In-gel Digestion and Mass Spectrometry Protein Identificationmentioning

confidence: 99%

“…Digestion with trypsin and subsequent spotting of peptide solutions onto the MALDI targets were performed automatically in an Ettan Spot Handling Workstation (GE Healthcare, Uppsala, Sweden). For preparation of MALDI-TOF-mass spectrometry analysis, protein spots were destained and digested in the gel with trypsin (Promega) and extracted, as described (29). The MALDI-TOF measurement of spotted peptide solutions was carried out on a 4800 MALDI TOF/TOF analyzer (Applied Biosystems, Foster City, CA).…”

Section: In-gel Digestion and Mass Spectrometry Protein Identificationmentioning

confidence: 99%

Nephrotic Syndrome and Subepithelial Deposits in a Mouse Model of Immune-Mediated Anti-Podocyte Glomerulonephritis

Meyer-Schwesinger

Dehde

Klug

et al. 2011

The Journal of Immunology

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Subepithelial immune complex deposition in glomerular disease causes local inflammation and proteinuria by podocyte disruption. A rat model of membranous nephropathy, the passive Heymann nephritis, suggests that Abs against specific podocyte Ags cause subepithelial deposit formation and podocyte foot process disruption. In this study, we present a mouse model in which a polyclonal sheep anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia, and elevated cholesterol and triglycerides. Development of proteinuria was biphasic: an initial protein loss was followed by a second massive increase of protein loss beginning at approximately day 10. By histology, podocytes were swollen. Electron microscopy revealed 60–80% podocyte foot process effacement and subepithelial deposits, but no disruption of the glomerular basement membrane. Nephrin and synaptopodin staining was severely disrupted, and podocyte number was reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage. Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the glomerular filtration barrier. Immunoelectron microscopy localized the Ab to podocyte foot processes and the glomerular basement membrane. Similarly, immunohistochemistry localized mouse IgG to the subepithelial space. The third complement component (C3) was detected in a linear staining pattern along the glomerular basement membrane and in the mesangial hinge region. However, C3-deficient mice were not protected from podocyte damage, indicating a complement-independent mechanism. Twenty proteins were identified as possible Ags to the sheep anti-podocyte serum by mass spectrometry. Together, these data establish a reproducible model of immune-mediated podocyte injury in mice with subepithelial immune complex formation.

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Prohibitin identified by proteomic analysis of prostate biopsies distinguishes hyperplasia and cancer

Cited by 78 publications

References 41 publications

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Proteomic analysis of differentially expressed proteins in normal human thyroid cells transfected with PPFP

Nephrotic Syndrome and Subepithelial Deposits in a Mouse Model of Immune-Mediated Anti-Podocyte Glomerulonephritis

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