Abstract
Hereditary colorectal cancer develops through a series of well-defined genetic and histological changes. However, elucidation of the canonical pathway based on hereditary colorectal cancer has not provided a clear explanation of the molecular mechanisms of sporadic colorectal cancer. To identify the alterative pathways involved in sporadic colorectal tumorigenesis, we performed gene expression analysis in patients with sporadic colorectal tumors. A comparison analysis of gene expression profiles revealed a pattern of upregulation of small proline rich repeat protein 3 (SPRR3) in tumor samples. SPRR3 has previously been reported to be downregulated in esophageal cancer. However, in the present study, we observed that SPRR3 was strongly upregulated in 31 of 35 samples of sporadic colorectal tumors (88%). We also determined that overexpression of SPRR3 not only accelerates colorectal cancer cell proliferation but also is associated with lymphovascular invasion in colorectal cancer. Moreover, AKT was activated and p53 levels were decreased in cells that overexpressed SPRR3. In contrast to the pattern seen in esophageal cancer, these results suggest that increased expression of SPRR3 is involved in colorectal tumorigenesis.
Highlights
The occurrence of colorectal cancer has gradually increased over the last decade, and colorectal carcinoma was the third most common cancer in Korea in 2005 [1]
When we investigated these genes, we found that small proline rich repeat protein 3 (SPRR3) was a protein associated with the molecular changes and clinicopathological features of this disease [8]
Loss of SPRR3 expression is frequently observed in esophageal squamous cell carcinoma (ESCC), where it is known to inhibit tumorigenesis (Supplementary Figure 1) [13,14,15]
Summary
The occurrence of colorectal cancer has gradually increased over the last decade, and colorectal carcinoma was the third most common cancer in Korea in 2005 [1]. Several oncogenes and tumor-suppressor genes are known to be involved in the progression of hereditary colorectal cancer, the molecular changes associated with sporadic colorectal cancer are not yet understood [2,3,4]. We previously identified several genes associated with molecular changes in sporadic colorectal cancers by microarray analysis of the gene expression profiles of sporadic colorectal cancer patients. When we investigated these genes, we found that SPRR3 (small proline rich repeat protein 3) was a protein associated with the molecular changes and clinicopathological features of this disease [8]. SPRR3 is frequently downregulated in esophageal squamous cell carcinoma (ESCC) and it has been shown to suppress the tumorigenicity of ESCC cells [13,14,15]
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