Expression of gap junction genes in astrocytes and C6 glioma cells

Naus, Christian C.; Bechberger, John F.; Caveney, Stanley; Wilson, John X.

doi:10.1016/0304-3940(91)90364-y

Cited by 114 publications

(72 citation statements)

References 23 publications

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“…In vivo observations indicating the influence of gap junctions on tumorigenesis are supported by in vitro data demonstrating the down-regulation of connexin expression and gap junction assembly in a wide range of neoplastic cell lines and primary tumours [14][15][16][17]. Furthermore, viral transfection was shown to reduce the levels of gap junctional coupling in cell populations, while a forced expression of genes encoding connexins inhibited the proliferation and affected the contact behaviour of transfected tumour cells [16].…”

Section: The Involvement Of Gap Junctions In the Regulation Of Tumourmentioning

confidence: 98%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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Tumour development is a process resulting from the disturbance of various cellular functions including cell proliferation, adhesion and motility. While the role of these cell parameters in tumour promotion and progression has been widely recognized, the mechanisms that influence gap junctional coupling during tumorigenesis remain elusive. Neoplastic cells usually display decreased levels of connexin expression and/or gap junctional coupling. Thus, impaired intercellular communication via gap junctions may facilitate the release of a potentially neoplastic cell from the controlling regime of the surrounding tissue, leading to tumour promotion. However, recent data indicates that metastatic tumour cell lines are often characterized by relatively high levels of connexin expression and gap junctional coupling. This review outlines current knowledge on the role of connexins in tumorigenesis and the possible mechanisms of the interference of gap junctional coupling with the processes of tumour invasion and metastasis. GAP JUNCTIONS -THEIR STRUCTURE AND BASIC FUNCTIONS IN TISSUE HOMEOSTASISGap junctions are aqueous intercellular channels which directly link the cytoplasmic compartments of adjacent cells (Fig. 1). These channels are formed upon the docking of two connexons, hexameric hemichannels built of proteins belonging to the connexin family [1]. Gap junctions are present in almost all vertebrate tissues, where they permit the intercellular exchange of small (< 1 kDa) metabolites and second messengers, and thus synchronise cellular functions in tissues [2][3][4]. Representative examples of the synchronising function of gap junctional coupling in tissues include electrical and metabolic coupling. In the former, gap junctions take part in the intercellular spreading of membrane depolarisation by permitting the rapid cell-to-cell transfer of calcium ions between cardiac muscle cells [1], or by constituting electrical synapses in the nervous system [5]. Metabolic coupling is established when the stimulation of one cell is propagated to a cluster of cells through the spreading of active substances, such as monosaccharides and cyclic nucleotides [2,6]. While electrical coupling predominantly synchronizes cell functions in excitable tissues, metabolic coupling affects the homeostasis of a spectrum of multicellular systems, including both excitable and non-excitable tissues. The crucial role of gap junctions in the regulation of tissue homeostasis is illustrated by the functional impairment of many vertebrate tissues occurring when there is deficient gap junctional communication [7,8]. For instance, disruption of the function of the gene encoding Cx32 is associated with the progressive degeneration of the peripheral nerves, resulting from the impairment of the diffusion of nutrients and signalling molecules between the perinuclear and periaxonal Schwann cell cytoplasm [for review see [9]. Furthermore, abnormalities have been observed in Cx32-deficient mouse livers: Cx32 disruption leads to a decrease in the disc...

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Section: The Involvement Of Gap Junctions In the Regulation Of Tumourmentioning

confidence: 98%

The stage-specific function of gap junctions during tumourigenesis

Czyż

2008

Cellular and Molecular Biology Letters

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“…4 In gliomas, the limited expression of gap junctions has been reported in cells of rat and human origin. 5,6 Although the molecular mechanisms underlying the antitumor role of Cx43 overexpression have not been elucidated, recent studies link the reversion of the transformed phenotype after Cx43 overexpression to a prolongation of G1 and S phases of the cell cycle and to a decreased expression of cell cycle regulatory genes, including cyclin A, D1, D2 and cyclin dependent kinases 5 and 6. 7 In vitro experiments have suggested that GJIC may also be one component of the so-called 'bystander effect', the phenomenon by which herpes simplex virus thymidine kinase (HSVtk)-transduced cells cause the death of nearby untransduced neoplastic cells when treated with ganciclovir (GCV).…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo effects of retrovirus-mediated transfer of the connexin 43 gene in malignant gliomas: consequences for HSVtk/GCV anticancer gene therapy

et al. 1998

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In tumors, gap junctional intercellular communication cantly more slowly than control U-87 cells and lose their (GJIC) is usually down-regulated and the expression of tumorigenicity when injected subcutaneously in nude mice. connexins, membrane proteins constituting gap junction When the Cx43 gene was transduced in vitro in U-87 cells channels, is often low or altered. GJIC, allowing the interby a retroviral producer cell line (N3.2.ii, titer cellular diffusion of ganciclovir (GCV) triphosphate, is also 1.5 × 10 6 c.f.u./ml) in vivo results were similar. However, one mediator of the 'bystander effect', the phenomenon by only when U-87 cells were co-injected with N3.2.ii cells in which herpes simplex virus thymidine kinase (HSVtk)-nude mice in a 1:5 ratio, a 50% reduction in tumor size transduced, neoplastic cells kill surrounding HSVtk-negawas obtained during the first 3 weeks. Moreover the cotive cells when treated with GCV. We set up experiments injection of U-87 cells with N3.2.ii and SBA cells (a retrovito evaluate the effects of retrovirus-mediated in vivo gene ral producer cell line expressing the HSVtk gene), was not transfer of connexin 43 in malignancies with low GJIC able to potentiate the effects of GCV administration, sugcapacity. We found that U-87 human glioblastoma cells gesting that Cx43 gene transfer requires more efficient transfected in vitro by the human Cx43 cDNA grow signifivectors to increase the bystander effect in vivo.

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“…11 Astrocytic gap junctions are mainly composed of the channel protein, connexin43 (Cx43). 12,13 Although Cx43-deficient mice [Cx43(Ϫ/Ϫ)] die immediately after birth, 14 heterozygous Cx43 null mice [Cx43(ϩ/Ϫ)] are viable. Cultured Cx43(ϩ/Ϫ) astrocytes exhibit reduced Cx43 protein expression and intercellular Ca 2ϩ signaling.…”

mentioning

confidence: 99%

Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes

Nakase

Söhl

Theis

et al. 2004

The American Journal of Pathology

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205

150

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Astrocytes secrete cytokines and neurotrophic factors to neurons, consistent with a neurosupportive role for astrocytes. However, in ischemic or metabolic insults, the function of astrocytic gap junctions composed mainly from connexin43 (Cx43) remains controversial. We have previously shown that heterozygous Cx43 null mice subjected to middle cerebral artery occlusion exhibited significantly enhanced stroke volume and apoptosis compared to wild-type mice. In this study, we used mice in which the human GFAP promoter-driven cre transgene deletes the floxed

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Expression of gap junction genes in astrocytes and C6 glioma cells

Cited by 114 publications

References 23 publications

The stage-specific function of gap junctions during tumourigenesis

The stage-specific function of gap junctions during tumourigenesis

In vitro and in vivo effects of retrovirus-mediated transfer of the connexin 43 gene in malignant gliomas: consequences for HSVtk/GCV anticancer gene therapy

Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes

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