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Comparative Proteomics of Colorectal Cancer: Abnormal Expression of Proteins within the Tumor Nest and Implication of HnRNP A1 as an Oncoprotein in Tumorigenesis

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Author(s): DaoHai Zhang | Lee Kian Tai | Ming Teh | Sunil K. Sethi | Evelyn S. C. Koay

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 2;
Issue: 1;
Start page: 17;
Date: 2006;
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Keywords: colorectal cancer | proteomics | drug target | hnRNP A1

ABSTRACT
AIM: To decipher the key biochemical modulators of tumorigenesis and evaluate the potential of candidate proteins as biomarkers or targets for novel therapeutic intervention of colorectal cancer (CRC).METHODS: Differentially expressed proteins in colorectal tumors were identified by gel-based proteomics, tandem mass spectrometry and NCBInr database interrogation, and further validated by Western blotting and immunohistochemical (IHC) staining. The associations of heterogeneous nuclear ribonucleoprotein (hnRNP A1) overexpression with other clinicopathologic features of CRC were assessed using a tissue microarray comprising 60 non-tumor tissue cores and 100 tumor tissue cores.RESULTS: Thirty proteins involving in diverse biological functions were identified. Up-regulation of proteins such as hnRNP A1, platelet-derived endothelial cell growth factor (PD-ECGF), destrin and proliferating cellular nuclear antigen (PCNA) were confirmed by Western blots. IHC staining showed that hnRNP A1 and PCNA were overexpressed in both the nuclei and cytoplasm of the tumor cells, while PD-ECGF was expressed in the endothelial cells within the cancer nest. Destrin was expressed in both tumor and non-tumor cells. The tissue microarray study revealed that hnRNP A1 was highly expressed in the cytoplasm in 80% (70 of 89) of tumors, but there was no association with tumor (Duke’s) stage, tumor differentiation, or lymph node metastasis.CONCLUSION: Our study demonstrates the complementation of proteomics and IHC techniques in identifying and localizing the differentially expressed proteins from both tumor and non-tumor cells in the in vivo tumor microenvironment. The novel oncoprotein hnRNP A1 could be a potential target for CRC treatment.
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