Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE

Pütz, Stephanie; Vogiatzi, Fotini; Stiewe, Thorsten; Sickmann, Albert

doi:10.1186/1476-4598-9-254

Cited by 28 publications

(39 citation statements)

References 49 publications

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“…It was shown that Prx6 is upregulated in patients with esophageal squamous cell carcinoma [70]. In contrast, previous proteomic analysis using malignant transformative cell models exhibited the downregulation of Prx6 [71]. Our data are similar to those on esophageal squamous cell carcinoma.…”

Section: Prx2supporting

confidence: 83%

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells

Su¹,

Lin

Chiu

et al. 2012

Electrophoresis

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The extracts from soft corals have been increasingly investigated for biomedical and therapeutic purposes. The aim of this study is to examine and analyze the anti-tumor effects of the genus Sinularia extract sinularin on A2058 melanoma cells using MTT assay, cell migration assay, wound healing assay, flow cytometric analysis, and proteomic analysis. Sinularin dose-dependently (1-5 μg/mL) inhibited melanoma cell proliferation while the treatment at identical concentrations suppressed cell migration. Sinularin dose-dependently enhanced apoptotic melanoma cells and caused tumor cell accumulation at G2/M phase, indicating that sinularin exerts apoptosis-induced and cell cycle-delayed activities in A2058 melanoma cells. Comparative proteomic analysis was conducted to investigate the effects of sinularin at the molecular level by comparison between the protein profiling of melanoma cells treated with sinularin and without the treatment. Thirty-five differential proteins (13 upregulated and 22 downregulated) concerning the treatment were identified by liquid chromatography-tandem mass spectrometry. Proteomic data and Western blot displayed the levels of several tumor inhibitory or apoptosis-associated proteins including annexin A1, voltage-dependent anion-selective channel protein 1 and prohibitin (upregulated), heat shock protein 60, heat shock protein beta-1, and peroxiredoxin-2 (downregulated) in A2058 melanoma cells exposed to sinularin. Increased expression of p53, cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, p21, and Bax and decreased expression of Bcl-2 in sinularin-treated melanoma cells suggest that the anti-tumor activities of sinularin against melanoma cells are particularly correlated with these pro-apoptotic factors. These data provide important information for the mechanisms of anti-tumor effects of sinularin on melanoma cells and may be helpful for drug development and progression monitoring of human melanoma.

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Section: Prx2supporting

confidence: 83%

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells

Su¹,

Lin

Chiu

et al. 2012

Electrophoresis

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“…In addition, an extended analysis of protein posttranslational modifications could provide additional insight, especially into the final step of the model, where few genes were differentially expressed. A classical proteomics strategy based on 2D PAGE analysis and isobaric tag for relative and absolute quantitation (iTRAQ) has earlier been used to study this fibroblast cell-line model and allowed the discovery of 201 differentially expressed proteins (35). Most of the proteins identified by Pütz et al could be confirmed by our study, although we were, thanks to the higher sensitivity of RNAseq, able to identify as many as 1,357 differentially expressed genes, corresponding to ∼6% of all human genes.…”

Section: Discussionmentioning

confidence: 99%

Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model

Danielsson

Skogs

Huss

et al. 2013

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

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The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a fourstage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that ∼6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.C ancer development is a multistep process where genetic changes are accumulated, thus progressively transforming cells into a cancerous phenotype (1, 2). Over the last decades, numerous investigators have studied the underlying molecular mechanisms for malignant transformation. This has resulted in many models that explain the development of a malignant phenotype of human cells, for instance the "hallmarks of cancer" by Hanahan and Weinberg (3,4).With new technologies for deep sequencing, novel opportunities to study the underlying molecular events leading to cancers have emerged. A large number of investigations have analyzed mutations occurring in tumors, such as the analysis of mRNA expression, microRNA expression, and DNA copy number in a large number of tumors in the Cancer Genome Atlas (5). Similarly, the Human Protein Atlas project (6) studies human cancers using a proteome-wide collection of antibodies, resulting in publicly available immunohistochemistry images covering 20 different human cancer types.An interesting approach to studying the molecular mechanisms underlying cancer is to use an isogenically matched cell model in which normal cells are progressively transformed into malignant cells. There are several studies where genetic elements such as oncogenes have been introduced to different types of cells in an accumulative order as an attempt to mimic the natural steps of transformation (7,8). One such cell model is the fourstage model based on BJ fibroblasts developed by the Weinberg group, in which primary fibroblast cells were immortalized with telomerase reverse transcriptase (...

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“…Expression analysis with oligonucleotide microarrays revealed that TRAP1 is one of the target genes elevated by the Myc oncogene (38). TRAP1 was over-expressed in primary human fibroblasts and mouse prostate by SV40-induced malignant transformation (39,40). Various cancer cell lines, including mouse adenocarcinoma, and specimens from human cancer patients also consistently showed over-expression of TRAP1, while it remained undetectable in normal cells and tissues (16,40).…”

Section: Regulation Of Trap1 and Mitochondrial Hsp90mentioning

confidence: 99%

TRAP1 regulation of mitochondrial life or death decision in cancer cells and mitochondria-targeted TRAP1 inhibitors

Kang¹

2012

BMB Reports

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Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE

Cited by 28 publications

References 49 publications

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells

Proteomic investigation of anti‐tumor activities exerted by sinularin against A2058 melanoma cells

Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model

TRAP1 regulation of mitochondrial life or death decision in cancer cells and mitochondria-targeted TRAP1 inhibitors

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