Differential Expression of Ribosomal Proteins in Human Normal and Neoplastic Colorectum

Abstract

S U M M A R Y Ribosomal proteins are a major component of ribosomes and play critical roles in protein biosynthesis. Recently it has been shown that the ribosomal proteins also function during various cellular processes that are independent of protein biosynthesis therefore called extraribosomal functions. In this study we have, for the first time, determined the expression profile of 12 ribosomal proteins (Sa, S8, S11, S12, S18, S24, L7, L13a, L18, L28, L32, and L35a) in normal epithelia of human colorectal mucosa using immunohistochemistry (IHC) and then compared their expression patterns with those of colorectal cancer. In the normal mucosa, ribosomal proteins were largely associated with the ribosomes of mucosal epithelia, and the expression level of ribosomal proteins, except for S11 and L7 proteins, was markedly increased in associated with maturation of the mucosal cells. On the other hand, these ribosomal proteins were markedly decreased in colorectal cancer compared with the normal mucosa. By contrast, S11 and L7 ribosomal proteins were rarely associated with the ribosomes of colorectal epithlia except immature mucosal cells, whereas their expression levels were significantly enchanced in colorectal cancer cells. In addition, L7 ribosomal protien was detected in the secretory granules of the enterochromaffin cells in the colorectal mucosa and in carcinoma cells expressing chromogranin A. These results indicate that the expression of ribosomal proteins is differentially regulated not only in normal mucosa but also in carcinoma of human colorectum, and suggest an extraribosomal function of L7 ribosomal protein in neuroendocrine function.

Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation

“…There are seven different S27 message isoforms all with identical coding regions but different tissue distributions, consistent with post-transcriptional regulation (Thomas et al 2000). Ribosomal proteins L7 and S11 are overexpressed in colorectal carcinomas (Kasai et al 2003), while the L13 protein, which has an identical protein-coding region to the breast basic conserved 1 protein (BBC1), is overexpressed in gastrointestinal cancer cells (Kobayashi et al 2006). RNAi knockdown of L13 significantly enhanced the sensitivity of these cells to DNA damage, while exogenous addition of L13 expression into cells inhibited chemosensitivity (Kobayashi et al 2006).…”

Ribosomal Proteins and Colorectal Cancer

“…The other 10 RPs exhibited a similar staining pattern that were more abundant in normal mucosa than CRC tissue, especially in columnar and goblet cells. Interestingly, these RPs were expressed more abundantly in mature epithelial cells of the upper crypts rather than the immature epithelial cells of the lower crypts, suggesting that the biosynthesis of these ribosomal proteins is significantly enhanced in association with maturation of the mucosal epithelia [31]. We constructed digital gene expression profiles for normal mucosa, colorectal adenoma and CRC by a bioinformatics method based on expressed sequence tag (EST) database (dbEST) of National Center for Biotechnology Information (NCBI) in 2005 [32].…”

“…Secondly, RPs showed different expression patterns: not the all RPs increased in the same tumor or tissue, and the same RP expressed differentially in different tumors or different stages of diseases. Thirdly, some RPs only increased in senescent cells, [38] some in quiescent cells and some in tumor cells well differentiated [31] but some decreased in metastatic CRC [29]. Fourthly, p53 mutation, a common event in CRC, which is considered the key factor in colon carcinogenesis can upregulate only several RPs but not all of them; [39] Fifthly, overexpression of specific RPs did not increase the synthesis of proteins [40].…”

Atypical protein kinase C (iota) activates ezrin in the apical domain of intestinal epithelial cells

“…This configuration is known as the 'active' form of ezrin (Fievet et al, 2004). In normal intestinal epithelial cells, ribosomes are concentrated in the perinuclear region, away from the subapical cytoplasm (Kasai et al, 2003). More importantly, in situ hybridization data on the distribution of ezrin mRNA in enterocytes suggests a diffuse, perhaps supranuclear distribution rather than apical localization of ezrin mRNA (Barilá et al, 1995).…”