Defining the molecular mechanisms involved in cancer formation and progression is still a major challenge in colorectal-cancer research. Our strategy was to characterize genes whose expression is altered during colorectal carcinogenesis. To this end, the phenotype of a colorectal tumour was previously established by partial sequencing of a large number of its transcripts and the genes of interest were selected by differential screening on high-density filters with mRNA of colorectal cancer and normal adjacent mucosa. Fifty-one clones were found over-expressed and 23 were underexpressed in the colorectal-cancer tissues of the 5 analyzed patients. Among the latter, clones 6G2 and 32D6 were found of particular interest, since they had significant homology with several homeodomain-containing genes. The highest degree of similarity was with the murine Cdx1 for 6G2, and with the murine Cdx2 and hamster Cdx3 for 32D6. Using a RT-PCR approach, complete sequence of both types of homeobox-containing cDNA was obtained. The amino-acid sequence of the human Cdx1 is 85% identical to the mouse protein, and human Cdx2 has 94% identity with the mouse Cdx2 and hamster Cdx3. Tissue-distribution analysis of Cdx1 and Cdx2 mRNA showed that both transcripts were specifically expressed in small intestine, in colon and rectum. Colorectal cancer is the second most common tumour in men and the third in women in the Western countries. Although much is known about the epidemiology, morphology and genetics of colorectal tumorigenesis, our knowledge of the perturbations of gene expression that occur in colorectal tumours remains limited. Such tumours may arise from benign adenomatous polyps, which later progress to adenocarcinomas through several molecular events. They thus provide a very useful paradigm for studying the molecular genetic bases of cancer. The multistep process leading to colorectal tumorigenesis probably involves the loss of function of tumour-suppressor genes, as well as the activation of oncogenes. Several important genes have already been identified, but they do not account for the whole process, and other genes are probably involved.Efforts have been made to characterize these genes. Differential hybridization techniques and screening of substracted libraries allowed the elucidation of some of them (Bartsch et al., 1986;Denis et al., 1993;Yow et al., 1988;Schweinfest et al., 1993;Kondoh et al., 1992; Barnard et al., 1992a, b). We developed an alternative strategy, in which the phenotype of a colorectal tumour was established by partial sequencing of a large number of randomly selected transcripts (Frigerio et al., 1995). This repertory of ESTs should therefore contain most of the differentially expressed genes. Recently, Nguyen et al. (1995) have developed an efficient method of differential screening in which cDNA clones are gridded on high-density colony filters and hybridized with complex probes derived from poly (A) 1 RNA from different cells or tissues. The signals observed are measured, providing a ''hybridization s...

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We are interested in the characterization of genes whose expressions in the colon are modified during colorectal carcinogenesis. Our approach was to establish the phenotype of a colon tumor by partial sequencing of a large number of transcripts, then to select mRNAs of potential interest by differential screening with complex probes from normal or cancerous colon. In this paper, we report the cloning and sequencing of a mRNA strongly underexpressed in colorectal cancer. It corresponded to a protein comprising 323 amino acids, that appeared to be human galectin-4 on the basis of 76% and 79% amino acid identity to the rat and pig counterparts, respectively. Tissue distribution analysis showed that its expression was restricted to the small intestine, colon and rectum. Galectin-4 expression was compared in tumor and normal adjacent colon of 19 patients. In 18 patients, the mRNA concentration was 1.5-50-times lower in the tumor. No significant correlation was observed between decreased expression of galectin-4 and the degree of differentiation of the tumor or Duke's state. These results suggest that decreased galectin-4 mRNA expression may be an early event in colon carcinogenesis. Among five cell lines derived from colon carcinoma, only two (HT29 and LS 174T) expressed galectin-4 mRNA.Keywords: lectin ; colorectal cancer ; differential screening ; mRNA expression ; expressed sequence tags.Changes in cell phenotype that occur during tumorigenesis are the result of qualitative and quantitative perturbations in gene expression. Loss of function of tumor-suppressor genes and activation of oncogenes are probably involved (Fearon and Vogelstein, 1990). Recently, efforts have been made to characterize other genes whose expressions are modified during colorectal cancer, with the hope of detecting molecules associated with the different stages of carcinogenesis. Differential hybridization techniques and screening of substracted libraries allowed descriptions of some of them. We have developed an alternative strategy in which the phenotype of a colorectal tumor was established by partial sequencing of a large number of randomly selected transcripts (Frigerio et al., 1995). This repertory of expressed sequence tags (ESTs) should, therefore, contain genes of interest. To select these genes, we used a differential screening where the cDNAs of our library were gridded on high-density colony filters and hybridized with complex probes prepared from poly(A)-rich RNA extracted from normal or cancerous colorectal tissue. Several clones corresponding to mRNAs overexpressed or under-expressed in cancer were identified. We describe in the present paper one clone selected because it was down-regulated in 18 out of 19 samples of colorectal cancer tissues. Sequencing demonstrated that it corresponded to human galectin-4 mRNA and analysis of its tissue distribution revealed specific expression in intestine.Galectins are the most widely expressed vertebrate lectins that bind galactosides (Barondes, 1988;Harrison, 1991 ;Lotan, 1992;Zhou and C...

We have established the phenotype of a colorectal tumor by partial sequencing of 2166 transcripts that were eventually arrayed on high‐density filters. These filters were used for differential screening with mRNAs of colorectal cancer and normal adjacent mucosa to characterize genes whose expression is altered in colorectal carcinoma. Three genes encoding related proteins, PAP, reg Iα and reg Iβ, were over‐expressed in cancer. Northern‐blot analysis confirmed that their expression was very low in normal colonic epithelial cells, but elevated in 75% of tumors. Western blotting with specific antibodies to pap and reg Iα revealed in tumors a single band of the expected size (15–16 kDa), demonstrating synthesis of the proteins. Pap was localized by immunohistochemistry to the cytoplasm of epithelial cells. In cancerous tissue, many cells showed a strong staining signal, but the proportion of stained cells was variable among patients. In normal mucosa, staining was light and restricted to a few cells scattered in the epithelium. Similar results were obtained with antibodies against reg Iα. No significant relationship was found between concentrations of pap, reg Iα or reg Iβ and clinical outcome. We looked at potential effectors of pap/reg gene over‐expression by testing, in 2 adenocarcinoma cell lines, the efficacy of the pap promoter at driving a reporter gene; strong induction was observed upon exposure to IFNγ and IL‐6. By analogy with observations in hepatocellular carcinoma, our results suggest that prevention of PAP/reg expression in normal colon cells by silencing their gene promoters is relieved during colon carcinogenesis, allowing their up‐regulation by mediators such as cytokines. Int. J. Cancer 81:688–694, 1999. © 1999 Wiley‐Liss, Inc.

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In Algeria, the CRC wing and become the first digestive cancer in both sexes, outperforming stomach cancer. To enrich the Algerian cancer registries, we analyzed the profiles of patients with these cancers in Jijel Willaya. This was a retrospective and descriptive analysis of epidemiological, clinicopathological and biological profiles of 62 CRC cases. We found that the CRC represented the first type of digestive cancers in which the three quarters were colon cancers. The most affected age group was 60-70 years with a male predominance and an average age of 56.20 years. The bleeding and abdominal pain were the majority telltale signs.The combined chemotherapy has been standardized with all patients and the Lieberkühnien adenocarcinoma was the major histological form. The disease issue and the choice of therapy depended on the K-RAS gene mutations. Our results were often compatible with the available literature and may provide reliable and relevant data on this disease.

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