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- Alaiya, Ayodele A
(författare)
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Cancer proteomics : characterisation of protein expression in human epithelial tumours
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Defining differences in protein expression between tumour cells of various degrees of malignancy is a first step in the development of markers for tumour diagnosis. In this thesis, the expression of multiple proteins in benign and malignant human ovarian, breast and prostate tumours was examined using two-dimensional gel electrophoresis (2-DE). We were able to show a similar pattern of expression of a set of ten proteins between benign and malignant cells in all three tumour types examined. Cytokeratins and high molecular weight tropomyosins were consistently down-regulated in carcinomas, whereas stress proteins (HSP90, HSP60 and calreticulin) were upregulated. This finding suggests a high degree of homology in the expression of these proteins among different tumour types of epithelial origin. An attempt to apply principal component analysis of quantitative 2-DE data for diagnosis of ovarian cancer is presented. Data of the expression of 170 polypeptides was compiled from 22 tumours and used to construct a model for classification into benign, borderline and malignant ovarian tumours. When the model was tested using 18 tumours, 11 tumours (61%) were correctly classified. We were encouraged by this result and intend to increase the number of tumours used to construct the model. Future work will show whether it is possible to accurately classify tumours by their gene expression profiles. Twenty proteins in the 2-DE maps of breast, lung and ovarian tumours were identified using mass spectrometry. Some of these proteins were found to consist of polypeptide fragments, suggesting the occurrence of proteolytic processing of polypeptides in these tumours. The process of tumour progression leads to the development of tumour heterogeneity. The 2-DE technique was used to study intra- and intertumour heterogeneity. Our results suggested that the degree of intertumour heterogeneity was substantial, whereas intratumoural variations were less pronounced. We conclude that 2-DE separation of proteins in human tumours can yield new information relevant to the understanding of tumour biology. We believe that this line of research will lead to improved diagnostic and predictive tools.
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| 2. |
- Carlén, Lina M, et al.
(författare)
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Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis.
- 2005
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Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 124:1
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a disease with considerable heterogeneity in clinical presentation. This is the first study using two-dimensional gel electrophoresis to compare global protein expression patterns in lesional and non-lesional skin from subjects with acute guttate psoriasis associated with streptococcal throat infection and chronic plaque psoriasis. Samples from experimentally induced contact eczema and normal skin from healthy controls were also included. Proteins with statistically significant differences in expression were used in hierarchical cluster analyses resulting in separation of the different samples into groups. Chronic plaque and guttate psoriasis samples were distinctly separated, indicating that they represent discrete phenotypes at the protein expression level. Interestingly, there was a trend in which guttate psoriasis lesions clustered closer to eczema than to chronic plaque psoriasis lesions, indicating that the duration of the inflammatory reaction may affect clustering. Several of the differentially expressed proteins were identified by mass spectrometry.
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| 3. |
- Hellman, Kristina, et al.
(författare)
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Differential tissue-specific protein markers of vaginal carcinoma
- 2009
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Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 100:8, s. 1303-1314
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Forskningsöversikt (refereegranskat)abstract
- The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin-proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.
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