Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18

Tanaka, Kiyoko; Oshimura, Mitsuo; Kikuchi, Rei; Seki, Madoka; Hayashi, Takako; Miyaki, Michiko

doi:10.1038/349340a0

Cited by 198 publications

(108 citation statements)

References 22 publications

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“…The strong prognostic value of 18q LOH for clinical course and survival of patients with CRC and the putative tumour-suppressive function of the DCC gene product (Tanaka et al, 1991) asks for the development of a method directly detecting the DCC gene product in CRC. As recently discovered by Hahn et al (1996), another putative tumour-suppressor gene, the DPC4 gene (deleted in pancreatic cancer locus 4), has been mapped to chromosome 18q21 very near to the DCC gene locus.…”

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confidence: 99%

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

Kr²,

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et al. 1998

Br J Cancer

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Summary Protein expression of the putative tumour-suppressor gene DCC on chromosome 18q was evaluated in a panel of 16 201. 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.Keywords: DCC; tumour-suppressor gene; loss of heterozygosity; colorectal cancer; immunohistochemistry; prognosis Genetic alterations in multistep colorectal tumorigenesis include loss of heterozygosity (LOH) of the putative tumour-suppressing DCC (deleted in colon carcinoma) gene on chromosome 18q21.1 Fearon et al, 1990;lacopetta et al, 1994 (Vogelstein et al, 1988). Recently, Jen et al (1995) have reported that the status of chromosome 18q has prognostic value for the clinical course and the survival of CRC patients giving patients with stage II cancer and 18q LOH a similar prognosis than patients with stage III cancer. Furthermore, 18q LOH correlates with an increased likelihood of distant metastasis (Kern et al, 1989) and is a strong predictive factor for deep muscle and lymphatic invasion (lino et al, 1994). In more than 90% of carcinomas with 18q allelic loss the deleted region includes the DCC locus . Reduced or missing mRNA expression was observed in more than 50% of CRC (Itoh et al, 1993) but a general mechanism for inactivation of the remaining allele has not yet been elucidated.The DCC gene encodes a neural cell adhesion-like transmembrane protein. Its extracellular region is composed of six immunoglobulin-like domains and four fibronectin-type III repeats. Functionally, the DCC gene product might control cell division and it might play a critical role in embryonic development

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confidence: 99%

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

Kr²,

Bm³

et al. 1998

Br J Cancer

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“…As shown in Figure 4, both DCC2 and DCC11 had slower growth kinetics characterized by a longer lag period after plating, and slower exponential growth rates as compared to parental HT29 and control Neo + cells. A decrease in growth kinetics has been reported in CoKFu cells transformed with the entire human chromosome 18, which harbors DCC (Tanaka et al, 1991).…”

Section: Expression a Ects The Growth Properties Of Ht29 Cellsmentioning

confidence: 93%

Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene

et al. 1999

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On 18q, frequently deleted in late stage colorectal cancers, a gene, Deleted in Colon Cancer (DCC), has been identi®ed and postulated to play a role as a tumor suppressor gene. DCC is retained in the majority of mucinous tumors, which produce high levels of mucins, and seems to be preferentially expressed in intestinal goblet cells. To investigate whether DCC is related to mucin expression and can modulate the transformed phenotype, we introduced a full-length DCC cDNA into HT29 cells, which can be induced in vitro to express MUC2, the gene that encodes the major colonic mucin. Expression of DCC did not modulate constitutive or induced expression of MUC2, nor did DCC induce a mature goblet cell phenotype. However, HT29 clones expressing high and low levels of DCC protein showed a signi®cant decrease in cell proliferation and tumorigenicity. Furthermore, increased shedding and an elevated rate of spontaneous apoptosis were associated with higher levels of expression of DCC. In summary, while restoration of DCC expression in a human colon carcinoma cell line did not in¯uence expression of di erentiation markers, DCC expression did a ect the growth and tumorigenic properties of the cells suggesting that DCC can modulate the malignant phenotype of colon cancer.

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“…The introduction of chromosome 8p into colon cancer cell lines has been shown to decrease their tumourigenecity and invasiveness. 21 Furthermore, LOH at 8p has been shown to correlate with the presence of micrometastases. 22 Halling et al found that in stage II and III CRCs 8p allelic imbalance was an independent prognostic indicator for decreased survival and time to recurrence.…”

Section: Colorectal Cancer Biologymentioning

confidence: 99%

Clinical significance of prognostic and predictive markers in colorectal cancer

2002

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Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18

Cited by 198 publications

References 22 publications

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

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

Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene

Clinical significance of prognostic and predictive markers in colorectal cancer

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