Connexin43 pseudogene is expressed in tumor cells and inhibits growth

Kandouz, Mustapha; Bier, Andrew; Carystinos, George D.; Alaoui‐Jamali, Moulay A.; Batist, Gerald

doi:10.1038/sj.onc.1207506

Cited by 80 publications

(61 citation statements)

References 40 publications

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“…ΨCx43 also has the capability of being translated in vitro when fused to green fluorescent protein. We also showed that ΨCx43 inhibited cell growth, similarly to Cx43 but in a gap junction-independent manner (28).…”

Section: Introductionmentioning

confidence: 72%

“…However, there is increasing evidence for the role of pseudogenes in cellular processes such as tumorigenesis (13)(14)(15). ΨCx43 is not only transcribed but is also capable of inhibiting cell growth and forming a functional protein when fused to green fluorescent protein in vivo (28). Detection of ΨCx43 in breast cancer cell lines and its inverse relationship with Cx43 protein led us to suspect a potential regulatory role of ΨCx43 on its homologue Cx43.…”

Section: Molecular Cancer Therapeuticsmentioning

confidence: 99%

“…Briefly, total RNA was isolated from cells using Trizol (Invitrogen) and Cx43-specific primers (forward, 5 ′ -ATGAG-CAGTCTGCCTTTCGT-3′; reverse, 5′-AAGGGTCGCTCT-TTCCCTTA-3′; Invitrogen); 10 ng of total RNA were synthesized into cDNA and amplified by PCR as mentioned previously (28). The total cycle number for the reaction was increased to 35 cycles.…”

Section: Cell Cultures and Stable Clonesmentioning

confidence: 99%

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Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target

Bier

Oviedo-Landaverde

Zhao

et al. 2009

Molecular Cancer Therapeutics

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Connexin43 (Cx43) is often deregulated in breast cancer tissue compared with normal adjacent tissue. Stable reexpression of Cx43 in cancer slows growth and renders the cells more sensitive to cytotoxic chemotherapeutics. Pseudogenes are often considered nonfunctional copies of DNA. The Cx43 pseudogene (ΨCx43) possesses all the features of an expressed gene and is exclusively transcribed in breast cancer cell lines and not in normal cells. ΨCx43 can be translated in vivo, and its protein exhibits growth-suppressive behavior similar to Cx43. We showed that ΨCx43 binds to the polyribosomes in breast cancer cells and that exogenous expression of ΨCx43 induces translational inhibition of Cx43. Furthermore, ΨCx43 is translated and binds more efficiently to the translational machinery than does Cx43 in an in vitro system. Following knockdown of ΨCx43 in breast cancer cells, we observed an increase in Cx43 RNA and protein. This results in increased cellular sensitivity to cytotoxic chemotherapy. Our results show that ΨCx43 acts as a posttranscriptional regulator of Cx43 in breast cancer cells, and that this represents an example of the regulation of genes by pseudogenes with potential therapeutic implications in cancer. [Mol Cancer Ther 2009;8(4):786-93]

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Section: Introductionmentioning

confidence: 72%

Section: Molecular Cancer Therapeuticsmentioning

confidence: 99%

Section: Cell Cultures and Stable Clonesmentioning

confidence: 99%

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Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target

Bier

Oviedo-Landaverde

Zhao

et al. 2009

Molecular Cancer Therapeutics

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“…37 In melanoma, the connexin protein, Cx43, has also been shown to be suppressed. 38 Our studies demonstrate that induced expression of Cx43 may help to increase the target area of plasma therapy which may occur through the bystander effect.…”

Section: Discussionmentioning

confidence: 99%

Preferential induction of apoptotic cell death in melanoma cells as compared with normal keratinocytes using a non-thermal plasma torch

Zucker

Zirnheld

Bagati

et al. 2012

Cancer Biology & Therapy

115

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“…2003; Kandouz et al . 2004). The parental gene product is peroxiredoxin‐6, an enzyme localised in lysosomes and active in lipid degradation pathways in various types of cells including alveolar macrophages (Sorokina et al .…”

Section: Discussionmentioning

confidence: 99%

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

et al. 2018

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SummaryGenetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non‐additive genetic variation, we present an approach using genome‐wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein–Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome‐wide markers were tested for associations between heterozygosity and bTB status using marker‐based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy‐Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome‐wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy‐number‐variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large‐scale data.

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Connexin43 pseudogene is expressed in tumor cells and inhibits growth

Cited by 80 publications

References 40 publications

Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target

Connexin43 pseudogene in breast cancer cells offers a novel therapeutic target

Preferential induction of apoptotic cell death in melanoma cells as compared with normal keratinocytes using a non-thermal plasma torch

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance

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