Reduced expression of deleted colorectal carcinoma (DCC) protein in established colon cancers

Abstract

Summary Using a bacterial fusion protein, a deleted colorectal carcinoma (DCC)-specific monoclonal antibody (MAb) 127-22 was established. Although MAb 127-22 reacted with almost all normal tissues, it did not react or only weakly reacted with many cancer cell lines, including colonic cancer lines, in flow cytometry. In Western immunoblots, the MAb reacted with a single 1 90-kDa molecule in a myeloma line Ara-10 extract. This component was scarcely detected in colonic cancer cell lines. Immunoblots of samples from 25 pairs of colonic cancers and adjacent normal tissues and from five adenoma tissues revealed that all normal colonic and adenoma tissues significantly expressed the DCC protein, whereas colonic cancer tissues showed poor expression. These results indicate not only deletion of and lowered mRNA expression of the DCC gene, but also marked reduction of DCC protein occurred in colonic cancer tissues. In addition, colonic cancer patients with liver metastasis expressed significantly lower levels of DCC than those without, suggesting the prognostic value of DCC expression.

DCC expression is related to mucinous differentiation but not changes in expression of p21WAF1/Cip1 and p27Kip1, apoptosis, cell proliferation and human papillomavirus infection in uterine cervical adenocarcinomas

“…Considering the significant difference in DCC expression between the two histological phenotypes, it was expected that reduced DCC expression may contribute to rapid tumour tissue kinetics, since a close association between de-regulation of this gene and tumour progression or metastasis has been reported in several human malignancies (Kikuchi-Yanoshita et al, 1992;Enomoto et al, 1995;Kong et al, 1997;Goi et al, 1998). Our results, however, revealed that DCC expression was not related to any cell kinetic markers or clinicopathological factors.…”

Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue

“…[11][12][13] In our study, we found no appreciable diVerences in the expression of DCC between the coeliac group and the controls.…”

“…Reduced immunohistochemical expression of the deleted in colorectal cancer (DCC) protein was noted in frank colon carcinoma, 12 13 whereas adenomas and normal colonic epithelium were found to express normal amounts of the DCC protein. 13 However, loss of heterozygosity at the DCC gene locus was recently noted in ulcerative colitis, with high grade dysplasia being associated with colorectal carcinoma.…”

Role of netrin-1 and netrin-1 dependence receptors in colorectal cancers

“…In more than 90% of primary colorectal cancers with LOH of chromosome 18q, DCC is included in the region of allelic loss (Fearon et al, 1990;Thiagalingam et al, 1996). Most studies have linked chromosome 18q LOH in colorectal cancers to a reduction in DCC expression both at the RNA level (Thiagalingam et al, 1996) and at the protein level (Goi et al, 1998). Loss of heterozygosity of chromosome 18q and/or decreased DCC expression have also been seen in various other cancers, including gastric, prostate, endometrial, ovarian, oesophageal, breast, testicular, glial, neuroblastoma and haematologic malignancies (see for review Mehlen and Fearon, 2004).…”