Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma

Brockmeyer, Phillipp; Hemmerlein, Bernhard; Jung, Klaus; Fialka, Florian; Brodmann, Tobias; Gruber, Rudolf; Schliephake, Henning; Kramer, Franz‐Josef

doi:10.3892/mco.2015.685

Cited by 6 publications

(7 citation statements)

References 32 publications

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“…connexin 43 (cx43), a member of the connexins family, is most abundantly expressed in the cardiac muscle (7). cx43 has been demonstrated to serve a role in a number of diseases, including oral squamous cell carcinoma, pancreatic cancer, prostate cancer, acute myeloid leukemia, myocardial edema, vascular restenosis and Parkinson's disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). cx43 is primarily a fast, low-resistance pathway that regulates electrical conduction between cardiomyocytes, coordinates mechanical and electrical activities of cardiac muscle and controls the conduction velocity of impulses to ensure that myocardial electromechanical activities are synchronized (18).…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

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Atrial fibrillation (AF) is the most common arrhythmia reported in clinical practice. Connexin 43 (Cx43) is a member of the connexin protein family, which serves important roles in signal transduction in vivo. The aim of the present study was to investigate the role of Cx43 in the induction and maintenance of atrial fibrillation by using an animal model of sympathomimetic atrial fibrillation. Cx43 was successfully knocked down in the myocardium with gene‑specific small interfering (si)RNA via lentiviral infection. A total of 25 dogs were randomly and evenly divided into five groups: Normal (N), rapid atrial pacing (RAP), isoproterenol (ISO) + RAP, RAP + Cx43 siRNA and ISO + RAP + Cx43 siRNA. The mRNA and protein levels, as well as the distribution of Cx43 on the cell membrane, were gradually decreased in each group compared with the N group following treatment (P<0.05). The induction rate of the atrial effective refractory period was not significantly affected in the RAP and RAP + Cx43 siRNA groups, whereas it was significantly reduced in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The induction rate of AF was gradually increased in the RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with the N group (P<0.05). The expression of nerve growth factor (NGF) and tyrosine hydroxylase (TH) was gradually increased in the ISO + RAP and ISO + RAP + Cx43 siRNA groups compared with their respective controls (RAP and RAP + Cx43 siRNA groups, respectively). However, no significant difference in the levels of NGF and TH was observed between the RAP, RAP + Cx43 siRNA, ISO + RAP and ISO + RAP + Cx43 siRNA groups. The mitochondrial morphology in each group was notably altered compared with the N group. The mitochondrial reactive oxygen species production and apoptotic index were gradually increased in each group compared with the N group (P<0.05). The results of the present study suggest that Cx43 reduces susceptibility to AF. Downregulation of Cx43 mediates the induction and maintenance of sympathetic AF.

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Section: Introductionmentioning

confidence: 99%

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

et al. 2018

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“…On the other hand, the higher frequency of the mutated G allele in the population identifies a population profile different from that described in countries such as Brazil for this SNP ( 18 ).…”

Section: Discussionmentioning

confidence: 69%

“…These results match those of Brockmeyer et al . in samples of OSCC patients ( 18 ). Studies in breast cancer showed that silencing Cx43 expression contributes to breast carcinogenesis, due to enhanced cell proliferation, lost cell polarity, misorientation of the mitotic spindle, and lost multilayer architecture of epithelial tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Cx43 is one of the potential biomarkers of tumorigenesis in the oral mucosa ( 18 ). Our results showed that this protein was not expressed in the membrane of cells from OSCC patient samples.…”

Section: Discussionmentioning

confidence: 99%

“…The reaction with all reagents excluding the template DNA was used as a negative control. The GJA1 C/G product (110 bp) was digested with Hae III (Thermo Fisher Scientific, Inc) at 37 °C for 3h, and the polymorphisms were determined as CC (110 bp), CG (57, 53, and 110 bp), or GG (53 and 57 bp) ( 18 ). The reaction having all the reagents excluding the genomic DNA was used as a negative control.…”

Section: Methodsmentioning

confidence: 99%

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Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Segura¹,

Secchi²,

Galíndez³

et al. 2022

Med Oral

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Background To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patients with oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredicTable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax, E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition. Material and Methods A cross-sectional study using genomic DNA and biopsy samples extracted from the oral mucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, Universidad Nacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797 by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test was applied to analyze immunostaining between controls/cases ( p <0.05 was set for statistical significance). Results GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation to CC “healthy” genotype ( p =0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in 75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis ( p =0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherin markers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, and Bax immunomarker was diminished in OSCC. Conclusions We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, which modifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G of GJA1rs12197797 could be at risk of developing OSCC. Key words: Cx43, E-cadherin, Ki67, Bax, Bcl-2, immunostaining expression profile, GJA1 rs12197797 genotyping.

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Lack of canonical activities of connexins in highly aggressive human prostate cancer cells

Asencio,

Véliz,

Flores-Faúndez

et al. 2024

Biol Res

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Connexins (Cxs) have the ability to form channels that allow the exchange of ions/metabolites between adjacent cells (gap junction channels, GJC) or between the intra- and extra-cellular compartments (hemichannels, HC). Cxs were initially classified as tumor suppressors. However, more recently, it has been shown that Cxs exert anti- and pro-tumorigenic effects depending on the cell and tissue context. In prostate cancer (PCa), the expression and functionality of Cxs remain highly controversial. Here, we analyzed the expression pattern of Cx26, Cx32, Cx37, Cx40, Cx43 and Cx45 in PCa cell lines with increasing levels of tumor aggressiveness (LNCaP < LNCaP-C4-2 < Du-145 < PC-3). In addition, GJ and HC activities were evaluated in the PCa cell lines using dye coupling and dye uptake assays, respectively. Lastly, the cellular localization of Cx26, Cx32, and Cx43 was analyzed in LNCaP and PC-3 cell lines using immunofluorescence analyses. Our results showed a positive association between the mRNA levels of Cx26, Cx37 and Cx45 and the degree of aggressiveness of PCa cells, a negative association in the case of Cx32 and Cx43, and no clear pattern for Cx40. At the protein level, a negative relationship between the expression of Cx26, Cx32 and Cx43 and the degree of aggressiveness of PCa cell lines was observed. No significant differences were observed for the expression of Cx37, Cx40, and Cx45 in PCa cell lines. At the functional level, only LNCaP cells showed moderate GJ activity and LNCaP and LNCaP-C4-2 cells showed HC activity. Immunofluorescence analyses confirmed that the majority of Cx26, Cx32, and Cx43 expression was localized in the cytoplasm of both LNCaP and PC3 cell lines. This data indicated that GJ and HC activities were moderately detected only in the less aggressive PCa cells, which suggest that Cxs expression in highly aggressive PCa cells could be associated to channel-independent roles.

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Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma

Cited by 6 publications

References 32 publications

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

Connexin 43, Bcl-2, Bax, Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Lack of canonical activities of connexins in highly aggressive human prostate cancer cells

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