COLON CANCER

Proteins Involved In Colon Cancer

Proteins Involved In Colon Cancer

Introduction

Colon cancer or Colorectal cancer (CRC2) is one of the most commonly occurring malignancies in both men and women. The poor prognosis for patients with advanced CRC has led to the intensive search for new technologies to enable earlier diagnosis and better treatment modalities. Whilst cDNA microarrays are able to analyze the expression of a large number of genes and to recognize patterns of gene expression in different diseases, application of this technique has been limited by the fact that the mRNA profile does not always represent the changes in protein expression within the tumor cell. Moreover, posttranslational modifications of proteins, which may be essential for protein function and activity, are not detectable by cDNA microarrays.

The complementary tools needed to identify the disease-specific proteins that are involved in malignant transformation and disease progression are being met by the rapidly evolving proteomics technologies.

Comparative analyses of the proteomes of normal and tumor tissues provide for a better understanding of the molecular events involved in tumor development, and are essential for developing more effective strategies for new biomarker and/or drug target discovery. Proteomic techniques include protein separation by two-dimensional gel electrophoresis (2-DE) and characterization by mass spectrometry of peptides, amino acid sequencing and bioinformatics analysis.

This platform has been widely used to unravel the critical changes and identify the cancer-related proteins in various cancers. The proteome investigation of CRC tissues has been intensively pursued, with most of the earlier studies employing 2-DE separation and MS analysis, and a 2-DE-derived protein database for human colon crypts and colon cancer cell lines has been built up and is accessible on the internet .

In two of these studies, liver fatty acid-binding protein and cyclooxygenase 2 were found to be downregulated in transformed colon mucosa whereas several members of the S100 protein family and one isoform of eukaryotic translation initiation factor 4H were upregulated.

Another study revealed more CRC-related proteins demonstrating differential expression in tumor tissues and colon cancer cell lines .

Proteome changes in colorectal tumor mucosa were also investigated using fluorescent dyes, a technique that enables detection and identification of the problematic low-abundance proteins, and many proteins involved in multiple functional categories were found to be differentially expressed in CRC. The functional proteomics of CRC has been well reviewed by Reymond et al.

Much more work towards unraveling the cellular and molecular mechanisms responsible for tumor cell growth, proliferation and disease progression in CRC remains to be done and many more protein effectors remain to be identified. A long-term aim of such research is to use the cumulative information of disease-related proteins in the processes of biomarker identification and targeted drug discovery. Here, we investigated the differential proteomes of six moderately differentiated CRC tumors and matched adjacent non-tumor mucosa.

To determine the distribution of proteins, ten pairs of paraffin-embedded CRC normal/tumor tissue blocks, which did not include the six pairs of frozen tissues used for the proteomic study, were sectioned and prepared for ...