Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours

Jamieson, Susan; Going, James J.; d’Arcy, Richard; George, W.D.

doi:10.1002/(sici)1096-9896(199801)184:1<37::aid-path966>3.0.co;2-d

Cited by 136 publications

(117 citation statements)

References 25 publications

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“…Consistently, it has been shown that re-expression of connexins in breast tumor cell lines can result in a partial cell re-differentiation to a more normal phenotype (Hirschi et al, 1996;Kalra et al, 2006;McLachlan et al, 2007), whereas downregulation of connexins in breast cell lines render them more migratory and invasive . However, a few studies have also reported an upregulation of connexins in breast cancer (Jamieson et al, 1998;Kanczuga-Koda et al, 2006;Naoi et al, 2007). Finally, it has been suggested that the role of connexins may differ depending of the type of tumor or its stage of progression, even favouring metastasis (McLachlan et al, 2007;Naus and Laird, 2010).…”

Section: Introductionsupporting

confidence: 81%

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

et al. 2010

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Gap junctions, the channels formed by the connexin (Cx) family of proteins, are responsible for direct intercellular communication. Although connexins are considered as tumor suppressors, their overall role in cancer onset, progression and metastasis is somewhat controversial. This study uses a novel Cx43 mutant mouse model (G60S mice) and cross-breeding strategies to determine the role of Cx43 in all stages of breast tumorigenesis. G60S mice were cross-bred with ErbB2 overexpressing mice, and spontaneous and 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumor development was evaluated. Mice were killed when tumors reached B1 cm 3 or when mice showed signs of critical illness. In both spontaneous and DMBA studies, onset of palpable tumors was delayed in G60S mice compared with mice in control groups. Moreover, while tumors from control mice reached the size threshold, most DMBA-exposed Cx43 mutant mice were killed prematurely because of labored breathing, independent of the presence of a palpable tumor. Reduced Cx43 levels in Cx43 mutant mice were accompanied by extensive mammary gland hyperplasia. Lung histology revealed that all Cx43 mutant mice exhibited mammaglobin-positive mammary gland metastases to the lung, and the number of metastases was increased by threefold in Cx43 mutant mice on treatment with DMBA. Thus, while reduced levels of Cx43 delayed the onset of palpable tumors, normal Cx43 levels inhibited mammary gland tumor metastasis to the lungs. Understanding the mechanisms of how Cx43, which is expressed primarily in myoepithelial cells, inhibits mammary gland tumor metastasis is critical as Cx43 is assessed as a candidate for therapeutic intervention.

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Section: Introductionsupporting

confidence: 81%

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

et al. 2010

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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 Tumoursupporting

confidence: 65%

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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“…L529S, L525S and L527S are cytoskeletal components. L513S, L520S and L521S are squamous cell speci®c markers ( (Jamieson et al, 1998), it remains to be seen if the L529S is a mutated or non-mutated form of connexin 26. L525S is plakophilin 1, a desmosomal protein found in plaque-bearing adhering junctions of skin (Moll et al, 1997).…”

Section: Tissue-specific Genesmentioning

confidence: 99%

Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysis

et al. 2000

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In order to develop eective vaccine products against human cancer, we are interested in identifying genes over-expressed in tumor cells. Through a combination of cDNA library subtraction and microarray technology, we identi®ed seventeen genes preferentially expressed in lung squamous cell carcinoma, including four novel genes. To date, expression pro®les of these genes were con®rmed by Northern and/or real-time analysis, and several genes were also found to be expressed in head and neck squamous tumors. Thus, these combined methods represent a high throughput approach for identifying tumor speci®c genes. Furthermore, the report of characterization on these genes will allow them to be exploited for their diagnostic, prognostic, and therapeutic potentials including immunotherapy and antibody based anticancer therapy. Oncogene (2000) 19, 1519 ± 1528.

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Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours

Cited by 136 publications

References 25 publications

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

The stage-specific function of gap junctions during tumourigenesis

Identification of genes differentially over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarray analysis

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