cDCC (Chicken homologue to a gene deleted in colorectal carcinoma) is an epithelial adhesion molecule expressed in the basal cells and involved in epithelial-mesenchymal interaction

Chuong, Cheng‐Ming; Jiang, Ting‐Xin; Yin, Eric; Widelitz, Randall B.

doi:10.1006/dbio.1994.1208

Cited by 45 publications

(29 citation statements)

References 21 publications

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“…Therefore, a similar role for Neogenin can be envisioned in adult tissues. Preliminary evidence suggests that DCC may also be involved in the di erentiation of stem cell populations within several epithelial tissues within the adult (Chuong et al, 1994). Therefore, the DCC/Neogenin subfamily of CAMs may play an integral role in regulating the di erentiation programmes and/or cell migration events within many adult and embryonic tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In the adult, DCC is expressed predominately in the central nervous system of the human and mouse. In addition, low levels of DCC expression have also been observed in some epithelial tissues including the gut of the chicken, the human colon, and the mouse bladder (Chuong et al, 1994;Hedrick et al, 1994;Reale et al, 1994, respectively). Although the presence of Neogenin protein has been demonstrated in adult chicken brain (Vielmetter et al, 1994), its expression pattern in non-neural tissues of the adult has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

“…Together, these two molecules de®ne a distinct subfamily of N-CAMlike cell adhesion receptors. Both DCC and Neogenin are expressed in the developing murine central nervous system and in the developing gut of the chick embryo (Chuong et al, 1994;Vielmetter et al, 1994;Cooper et al, 1995;Keino-Masu et al, 1996). In the adult, DCC is expressed predominately in the central nervous system of the human and mouse.…”

Section: Introductionmentioning

confidence: 99%

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Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis

1997

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Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of DCC or Neogenin in non-neuronal tissues in vertebrates. To gain an understanding of Neogenin function outside of the nervous system we have cloned and sequenced the mouse homologue of Neogenin. We describe three alternatively spliced exons within the extracellular domain of Neogenin and a fourth alternatively spliced exon within the cytoplasmic domain. We further demonstrate that three of these alternatively spliced exons are developmentally regulated. Analysis of Neogenin mRNA expression showed that two distinct Neogenin transcripts are expressed at signi®cant levels in a broad spectrum of adult mouse tissues and throughout the mid to late stages of embryogenesis. In situ hybridization studies on day 15.5 mouse embryos revealed that Neogenin is expressed widely throughout the developing mouse embryo, in both neuronal and nonneuronal tissues. These observations suggests that Neogenin may play an integral role in regulating di erentiation programmes and/or cell migration events within many embryonic and adult tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis

1997

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“…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 and cell differentiation (Edelman and Crossin, 1991;Chuong et al, 1994;Hedrick et al, 1994). As shown recently by Keino-Masu et al (1996) in neural tissue, DCC is a netrin receptor that is required for the guidance of developing axons.…”

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confidence: 93%

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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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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“…32 However, DCCmediated cell aggregation has not been clearly proven. 33 In addition to its putative role in neoplasia, DCC also mediates axon guidance and cell survival during neural development. As the nervous system develops, migrating axons and cells receive guidance cues that originate from several sources, such as members of the netrin, semaphorin, ephrin, and slit protein families.…”

Section: Introductionmentioning

confidence: 99%

Receptors that mediate cellular dependence

2005

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Cells depend for their survival on stimulation by trophic factors and other prosurvival signals, the withdrawal of which induces apoptosis, both via the loss of antiapoptotic signaling and the activation of proapoptotic signaling via specific receptors. These receptors, dubbed dependence receptors, activate apoptotic pathways following the withdrawal of trophic factors and other supportive stimuli. Such receptors may feature in developmental cell death, carcinogenesis (including metastasis), neurodegeneration, and possibly subapoptotic events such as neurite retraction and somal atrophy. Mechanistic studies of dependence receptors suggest that these receptors form ligand-dependent complexes that include specific caspases. Complex formation in the absence of ligand leads to caspase activation by a mechanism that is typically dependent on caspase cleavage of the receptor itself, releasing proapoptotic peptides. Cellular dependence receptors, considered in the aggregate, may thus form a system of molecular integration, analogous to the electrical integration system provided by dendritic arbors in the nervous system.

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cDCC (Chicken homologue to a gene deleted in colorectal carcinoma) is an epithelial adhesion molecule expressed in the basal cells and involved in epithelial-mesenchymal interaction

Cited by 45 publications

References 21 publications

Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis

Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis

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

Receptors that mediate cellular dependence

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