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At least 19 recordsLinked to original sources
PubMed1997

Alterations of the tumour suppressor gene DCC in neuroblastoma.

The deleted in colorectal carcinoma (DCC) gene, a candidate tumour suppressor, might be inactivated in a number of human cancers. In order to evaluate the possible role of DCC alterations in the pathogenesis of neuroblastoma, we examined 25 neuroblastoma cell lines and 16 primary tumours, including 6 samples with loss of heterozygosity (LOH) at the DCC locus for DCC mRNA expression, by using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The level of DCC expression was significantly reduced or undetectable in 12 of 25 (48%) cell lines and 7 of 16 (44%) primary tumours, suggesting that inactivation of the DCC gene is involved in the development of neuroblastoma. Three of the 6 tumours with LOH at the DCC locus revealed reduced DCC mRNA expression, indicating that LOH at the DCC locus might have affected the levels of DCC mRNA. We also screened for mutations in 4 exons of the DCC gene in 12 cell lines by using PCR-single strand conformation polymorphism (PCR-SSCP) analysis. Point mutations were not found except a polymorphic change at codon 201. The mechanism for inactivation of the DCC gene will be further investigated.

Genes, DCC↗
PubMed1992

Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma.

The development of colon carcinomas is associated with allelic deletions on chromosomes 5q, 17p, and 18q. The DCC gene located on chromosome 18q21.3 codes for a potential tumor suppressor gene related to cellular adhesion receptors. We investigated the expression of this gene in several pancreatic carcinoma cell lines and in patients with ductal adenocarcinomas of the pancreas. In 8 of 11 cell lines and in 4 of 8 primary tumors a complete extinction of DCC gene expression was observed, whereas the c-Ki-ras gene was mutated at codon 12 in 7 of 8 tumors. A highly reduced or absent expression of DCC was found in all low or undifferentiated pancreatic tumor cell lines, whereas in the more differentiated ones DCC expression was conserved. These data suggest that loss of DCC gene expression is an important factor in the development or progress of pancreatic adenocarcinoma and may be linked to the differentiated phenotype of the pancreatic tumor cell.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed1994

The DCC gene product in cellular differentiation and colorectal tumorigenesis.

The analysis of human colorectal tumors has revealed frequent loss of heterozygosity (LOH) of the long arm of chromosome 18. A novel gene, DCC (deleted in colorectal cancer), located within the region of LOH on chromosome 18q was identified and has been implicated as a tumor suppressor gene. We have now shown that DCC encodes a membrane-bound protein of the immunoglobulin-CAM family, as demonstrated by cell-surface labeling, immunohistochemical analysis, and sequencing of cDNA clones. The DCC protein was found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lacked DCC expression and loss of a chromosome 18q allele was often accompanied by loss of DCC expression in colon tumors. These results provide evidence that DCC encodes a cell surface-localized protein and emphasize the inverse relationship between differentiation and tumorigenesis.

Adenocarcinoma, Mucinous↗
PubMed1998

The significance of the expression of tumor suppressor gene DCC in human gliomas.

Deleted in colorectal carcinoma (DCC) gene has been as a candidate of tumor suppressor genes, has been identified recently and is thought to relate to the metastatic potential in some cancers. We examined the gene in 60 human gliomas (26 glioblastomas multiforme (GBMs), 16 anaplastic astrocytomas (AAs), 6 low grade astrocytomas (LGAs) of WHO Grade II, and 11 recurrent gliomas) and A172 human GBM cell line by reverse transcription polymerase chain reaction (RT-PCR). Twenty (77%) GBMs, 11 (69%) AAs, and 1 (17%) LGA revealed the reduced or absent DCC expression. Reduced DCC expression was also shown in 10 (91%) recurrent gliomas. Furthermore, in 5 cases with both primary and recurrent GBM, the DCC expressions of all recurrent tumors were lower than those of primary tumors. No significant correlation between DCC expression and Mib-1 labeling index was confirmed. The survival rate of patients without reduced DCC expression was significantly superior to that of patients with reduced DCC expression in overall malignant astrocytic tumors. In GBM and AA separately, DCC expression also tended to correlate with patient's prognosis. These results suggest that reduced DCC expression is an important marker in tumor malignancy and recurrence in astrocytic tumors and that may be a useful prognostic factor in patients with malignant astrocytic tumors.

Adolescent↗
PubMed1998

Detection of the DCC gene product in normal and malignant colorectal tissues and its relation to a codon 201 mutation.

Protein expression of the putative tumour-suppressor gene DCC on chromosome 18q was evaluated in a panel of 16 matched colorectal cancer and normal colonic tissue samples together with DCC mRNA expression and allelic deletions (loss of heterozygosity, LOH). Determined by a polymerase chain reaction (PCR)-LOH assay, 12 of the 16 (75%) cases were informative with LOH occurring in 2 of the 12 cases. For DCC mRNA, transcripts could be detected in all analysed normal tissues (eight out of eight) by RT-PCR, whereas 6 of the 15 tumours were negative. DCC protein expression, investigated by immunohistochemistry using the monoclonal antibody 15041 A directed against the intracellular domain, was homogeneously positive in all normal tissue samples. In tumour tissues, no DCC protein was seen in 11 out of 16 samples (69%). For the DCC codon 201, we found a loss of a wild-type codon sequence caused by mutation or LOH in at least 8 out of 15 cases (53%) compared with the corresponding normal tissue. DCC protein expression was undetectable in eight of the nine tumours missing both wild-type codons. Only one of the five tumours with retained DCC protein expression had no detectable wild-type codon 201. In addition, 9 out of 15 normal tissue specimens were mutated in codon 201. In two out of three cases with homozygous wild-type codons in peripheral blood lymphocyte (PBL) DNA, mutations were already observed in the tumour adjacent normal colonic mucosa. We conclude that DCC immunostaining should be introduced in the clinicopathological routine because of its strong correlation with the known prognostic markers 18q LOH and mutation of codon 201.

Blotting, Southern↗
PubMed1999

Morphological and functional effects of antisense RNA to the deleted in colorectal carcinoma (DCC) gene in a pancreatic carcinoma cell line.

To investigate the role of the deleted in colorectal carcinoma gene (DCC) in cells of pancreatic origin (MiaPaCa-2) we established cell lines stably expressing DCC antisense RNA. Expression of DCC antisense RNA led to striking alterations in the MiaPaCa-2 cell line. Antisense transfectants had nearly lost adherence and had acquired a spherical morphology. The ordered structure of actin bundles in the parental cell line had been lost largely in DCC antisense RNA expressing cell clones. Moreover, the antisense DCC transfected cells displayed a decreased growth rate, a decrease of cells in G1 phase and an accumulation in S phase of the cell cycle. These heavily altered characteristics of MiaPaCa-2 cells expressing DCC antisense RNA point to a yet unknown role for DCC in an important intracellular pathway.

Carcinoma, Ductal, Breast↗
PubMed1997

Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.

The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.

Animals↗
PubMed1993

Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas.

The putative tumor suppressor gene DCC has been shown to be frequently lost or expressed at low levels in colorectal, gastric, pancreatic, and esophageal carcinomas. In the present study, the DCC gene and its mRNA expression in human and rat prostatic carcinoma cells as well as in prostatic carcinoma tissues were examined by reverse transcriptase-polymerase chain reaction and polymerase chain reaction-loss of heterozygosity. The DCC gene was present and expressed in normal prostatic cells. However, its expression was decreased or undetectable in all prostatic carcinoma cells from either humans (4 cell lines) or rats (5 cell lines). In patients, 12 of 14 cases (86%) showed reduced DCC expression and 5 of 11 informative cases (45%) showed loss of heterozygosity at the DCC locus. These results demonstrate that loss of DCC expression and loss of heterozygosity at the DCC locus are a frequent feature of prostatic carcinoma cells.

Alleles↗
PubMed1994

Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis.

Since tumor suppressor gene DCC exhibits amino acid sequence homology to the neural cell adhesion molecule, there is a possibility that DCC might be related to tumor metastasis. In the present study, we examined 51 cases of primary esophageal carcinomas with regard to point mutations and loss of the DCC gene. We detected point mutations in two cases by screening using polymerase chain reaction-single strand conformation polymorphism analysis. When we determined the sequences, one case with lymph node metastasis showed an ATG (Met) to ACG (Thr) missense mutation in codon 168. Another case showed a CGA (Arg) to GGA (Gly) mutation in codon 201, which might be a polymorphic change, and two other mutations resulting in no amino acid change. We also examined loss of heterozygosity of the DCC gene. Forty-four of the 51 cases (86%) were informative, and among them 10 cases (23%) showed allelic deletion. The further away the lymph node metastasis was from the primary tumor, the higher the frequency of allelic deletions became. We also found allelic deletions in moderately and poorly differentiated squamous cell carcinomas but not in well differentiated ones. These results indicate that alterations of the DCC gene are related to the degree of lymph node metastasis and the degree of differentiation.

Alleles↗
PubMed1992

[DCC gene and leukemia].

The deleted in colorectal carcinomas (DCC) gene, located in human chromosome band 18q21, was identified as a potential tumor suppressor gene by Fearon et al. in 1990. The DCC gene encodes a protein which is highly similar to neural cell adhesion molecules and other related cell surface glycoproteins. In colorectal carcinoma, the expression of the DCC gene is reduced or absent in 88% of cases. We examined the expression of the DCC gene using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Its expression was reduced or absent in some leukemias. Our findings suggest the possibility that this gene may play a role in leukemogenesis.

Base Sequence↗
PubMed1995

The deleted in colorectal cancer (DCC) gene: a candidate tumour suppressor gene encoding a cell surface protein with similarity to neural cell adhesion molecules.

Chromosome 18q is among the regions thought to harbour a tumour suppressor gene(s) that is frequently inactivated by LOH during the development of several cancer types, including those of the gastrointestinal tract. In addition, colorectal cancers with 18q LOH have been shown to have a more aggressive clinical behaviour than those without 18q LOH. A candidate tumour suppressor gene from 18q, called DCC, has been identified. The DCC gene is contained within the common region of LOH on 18q, its expression is markedly decreased or absent in the majority of colorectal cancers and cell lines and somatic mutations within the DCC gene have been identified in a subset of cases. Thus, DCC represents the strongest candidate tumour suppressor gene on 18q. At present, however, many questions remain regarding the mechanisms underlying the inactivation of DCC and its decreased expression in cancers. The predicted structural similarity of DCC to the NCAMs suggests that it may function through cell-cell and/or cell-extracellular matrix interactions; however, little is known regarding the specific cellular function(s) of DCC. Many reports have detailed the alterations in phenotype observed in cancer cells, including changes in cell morphology and tissue architecture, loss of differentiated phenotype, decreased cell adhesion and aggregation, increased motility and invasive behaviour. These altered properties are likely to account in part for the invasive and metastatic properties of cancer cells in the patient. It is hoped that further studies will identify the means by which DCC inactivation may contribute to the altered growth properties of advanced cancer cells.

Alternative Splicing↗
PubMed1995

[Expression and loss of heterozygosity of DCC gene in human lung cancer].

The level of DCC mRNA expression was evaluated in tissue specimens from lung cancer patients by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) combined with Southern blot analysis. Obvious reduction of DCC gene expression was observed in 4 of 7 specimens (55%). In two specimens DCC transcript could only be detected after Southern blot hybridization of RT-PCR product. The average level of DCC expression in cancer tissue was about 45% of normal tissue as estimated by laser densitometer. We also studied DNA samples for loss of heterozygosity (LOH) at DCC locus at two polymorphic sites. Among the 15 specimens including 7 samples for RT-PCR, 9 (60%) were informative at either of two polymorphic sites. LOH was observed in 5 (55%). Two at the MspI-RFLP (restriction fragment length polymorphism) site and 3 at the site of VNTR (variable number of tandem repeat). These results suggest that allele loss and decreased expression of DCC gene are frequent events and the possible involvement of DCC gene in the pathogenesis of human lung cancer.

Adenocarcinoma↗
PubMed1995

Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract.

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract.

Adenocarcinoma↗
PubMedDate not supplied

Codon 201(Gly) polymorphic type of the DCC gene is related to disseminated neuroblastoma.

The deleted in colorectal carcinoma (DCC) gene is a potential tumor-suppressor gene on chromosome 18q21.3. The relatively high frequency of loss of heterozygosity (LOH) and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly) at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg) to GGA (Gly) at codon 201 resulting in three types of polymorphism: codon 201(Gly) type, codon 201(Arg/Gly) type, and codon 201(Arg) type. The codon 201(Gly) type occurred more frequently in disseminated (stages IV and IVs) neuroblastomas (72%) than in localized (stages I, II, and III) tumors (48%) (P=.035), and normal controls (38%) (P=.024). In addition, the codon 201(Gly) type was significantly more common in tumors found clinically (65%) than in those found by mass screening (35%) (P=.002). The results suggested that the codon 201(Gly) type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

Adolescent↗
PubMed1998

Loss of heterozygosity and loss of expression of the DCC gene in gastric cancer.

AIM: To investigate the role of DCC gene inactivation in the development and progression of gastric cancer. METHODS: Loss of heterozygosity and loss of expression of the DCC gene was studied in 51 surgical specimens of gastric cancer using detection based on polymerase chain reaction. RESULTS: Loss of heterozygosity was found in 35.3% (18 of 51) of specimens and was detected more often in stage III and IV (50%) than in stage I and II cancers (14.3%) (p < 0.05). Occurrence of loss of heterozygosity was not correlated with histological type, tumour size, depth of invasion, or lymph node metastasis. Loss of expression was found in 49% of cases (25 of 51). Loss of expression was not significantly correlated with any clinicopathological variable. CONCLUSIONS: Loss of heterozygosity and loss of expression of the DCC gene are often encountered in gastric cancer. Loss of heterozygosity of the DCC gene is a late event and associated with malignant progression.

Gene Expression↗
PubMed1997

Frequent reduction or loss of DCC gene expression in human osteosarcoma.

The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate tumour-suppressor gene that encodes for a transmembrane protein with strong structural similarity to members of the superfamily of neural cell adhesion molecules. It has been mapped to the chromosomal region 18q21.1 and it is implicated in cellular differentiation and developmental processes. In human osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18, suggesting a possible involvement of the DCC gene in the pathogenesis of this tumour entity. In the present study the mRNA and protein expression and rearrangements at the DNA level of the DCC gene were addressed in 25 osteosarcomas and several tumour cell lines, including osteosarcoma- and colon carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain reach in (RT-PCR)-based approach DCC expression was found to be lost or substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower grade osteosarcomas and most of the tumour cell lines, in contrast to normally differentiated osteoblasts. Immunohistochemical studies on DCC protein expression of 14 selected tumours correlated well with the RT-PCR-based results. In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas.

Adolescent↗
PubMed1993

Expression of the tumor suppressor gene DCC in human gliomas.

Reduced expression and/or allelic loss of the putative tumor suppressor gene DCC has been demonstrated in colorectal, gastric, pancreatic, esophageal, breast, and hematological malignancies. We examined the expression of the DCC gene in 22 tissue samples from human gliomas (glioblastoma multiforme, oligodendroglioma, and mixed oligodendroglioma/astrocytoma). Seven of 8 glioblastomas multiforme (88%) had reduced or absent DCC expression, and 8 of the other 14 tumors underexpressed DCC when compared to normal brain tissue. These results demonstrate that reduced expression of DCC occurs in human malignant gliomas and may be part of a common genetic pathway leading to neoplastic transformation and/or tumor progression.

Adult↗
PubMed1999

Reduced expression of APC and DCC gene protein in breast cancer.

AIMS: To investigate if the adenomatous polyposis coli (APC) protein and the deleted in colorectal cancer (DCC) protein expression can be demonstrated by an immuno-histochemical method and to study the role of APC and DCC gene inactivation in the development and progression of breast cancer using colorectal cancer as a control model. METHODS AND RESULTS: The reduced or loss of protein expression of the APC and DCC genes was studied in 27 surgical specimens of primary breast cancer using an immunohistochemical method. Reduced or lost expression was identified in 11 out of 27 samples (40.7%) for the APC gene and 15 out of 27 samples (55.6%) for the DCC gene. No statistically significant difference was observed between the reduced or lost protein expression and the histological grading of breast tumour for both the APC and the DCC gene. CONCLUSIONS: Both gene proteins can be demonstrated by the immunohistochemical method. Reduced or loss of APC and DCC gene product were observed in 40.7% and 55.6% cases of primary breast cancer respectively. Further work is required to investigate the significance of the finding.

Adenomatous Polyposis Coli Protein↗