| By analyzing gene expression profiles in human esophageal squamous cell carcinoma (ESCC), we identified 92 differentially expressed genes including 77 down-regulated and 15 up-regulated genes in cancer tissues compared with their normal counterparts. To validate the quality of our array data, a subset of six genes differentially expressed were examined using semi-quantitative RT-PCR and Western blot analysis. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins [SPRRs (SPRR1A, SPRR1B,SPRR2A, SPRR3)], calcium-binding S100 proteins [S100A8, S100A9], transglutaminase 3, cytokeratins [KRT4, KRT13], gut-enriched Krupple-like factor [GKLF] and cystatin A. Interestingly, most of the down-regulated genes, mapped to chromosomal 1q21, encoded Ca2+-binding or -modulating proteins that constitute cell differentiated complex. The transcription factors including GKLF and AP-1 might orchestrate the pattern of differentiation-associated genes expression in esophageal carcinogenesis. Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein [SPARC], cathepsin B and KRT17. Down-regulated polycystic kidney protein-1 [PKD-1], Annexin I and Annexin II might be involved in the calcium-channel, facilitating cell proliferation and differentiation. This study suggests that squamous cell differentiation-associated genes play an important role in ESCC initiation and progression.According to our gene expression profiles, S100A8 and S100A9 were identified as down-regulated genes in ESCCs. To further confirm their status in this malignancy, we analyzed their expression in 34 esophageal dysplasias, 18 carcinoma in situ, 19 intraepithelial and submucosal carcinomas and 81 advanced carcinoma specimens by immunohistochemical analysis. Frequent reduction of their expression was observed in a...
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