"Eine vergleichende Genexpressionsanalyse von Gap- Junction- Strukturproteinen in oralen Plattenepithelkarzinomen und gesunder Schleimhaut"

A comparative gene expression study of gap-junction proteins in oral squamous cell carcinomas and normal mucosa

by Tobias Brodmann
Doctoral thesis
Date of Examination:2012-04-23
Date of issue:2012-03-26
Advisor:Dr. Dr. Florian Fialka
Referee:Prof. Dr. Dr. Franz-Josef Kramer
Referee:Prof. Dr. Felix Hermann Brembeck
Referee:Prof. Dr. Patricia Virsik-Köpp
Persistent Address: http://dx.doi.org/10.53846/goediss-1201

 

 

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Abstract

English

Background: Gap junctional intercellular communication (GJIC) and connexin (Cx) expression are associated with cell-cycle control. Differential expression of connexins may therefore be indicative for malignant transformation of tissues. The aim of this study was to test the hypothesis that connexins are differentially expressed in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa.Methods: In carcinoma and mucosa samples of 15 patients with OSCC differential gene expression of connexin subtypes Cx26, Cx30, Cx30.3, Cx31, Cx31.1, Cx40, Cx43 and Cx45 was measured by quantitative real-time PCR. The interaction between different clinical parameters (tumor size, nodal status, AJCC stage, grading, gender, alcohol and tobacco consumption) on differential connexin expression was analyzed.Results: Cx45 was significantly overexpressed in OSCC tissue followed by Cx30.3. Cx26 and Cx31.1 were suppressed by trend but not significantly regulated after Holm-adjustment. Cx45/Cx43 ratio was significantly increased. Significant interactions between differential connexin expression and the parameters tobacco- or alcohol consumption were not found. Cx45 overexpression remained unchanged in different tumor stages.Conclusions: Certain subtypes of connexins as components of GJIC are differentially regulated in OSCC. It is hypothesized that overexpression of Cx45 may be responsible for a decreased GJIC and suppressed contact-inhibition by forming less conducting heteromeric Gap Junctions in colocalization with Cx43. Cx-regulation on transcriptional level appears to be an early effect in initiation or promotion of OSCC and is maintained during further progression of primary tumor sites.
Keywords: connexin; connexins; gap junction; GJIC; Cx 45; Cx 26; Cx-45; Cx-26; oral squamous cell carcinoma; carcinogenesis; OSCC; gene expression; comparative gene expression

Other Languages

Mit der Fragestellung, inwiefern Connexine in humanen oralen Plattenepithelkarzinomen exprimiert werden und sich diese Expression in Bezug auf gesunde Schleimhaut im intraindividuellen Vergleich unterscheidet, wurde eine quantitative real-time PCR-Analyse durchgeführt. Die differentielle Genexpressionsanalyse an n=15 Patienten umfasste die folgenden Connexinsubtypen: Connexin 26, Connexin 30, Connexin 30.3, Connexin 31, Connexin 31.1, Connexin 32, Connexin 40, Connexin 43, Connexin 45 und Connexin 50. Connexin 32 und Connexin 50 wurden in oraler Mukosa und in oralen Plattenepithelkarzinomen nicht exprimiert. Es konnten 8 Connexinsubtypen identifiziert werden, von denen gezeigt werden konnte, dass sie physiologischerweise in oraler Schleimhaut exprimiert werden: Connexin 26, Connexin 30, Connexin 30.3, Connexin 31, Connexin 31.1, Connexin 40, Connexin 43 und Connexin 45. Davon zeigte Connexin 45 in Tumorgewebe eine signifikante Überexpression, Connexin 26 war tendenziell unterexprimiert. Eine Korrelation mit klinischen Parametern, wie beispielsweise Tumorstadium, bestand nicht
Schlagwörter: Connexin; Connexine; Gap Junction; oral;Plattenepithelkarzinom; PEC; Genexpression; Expression; Karzinogenese; GJIC; Cx 45; Cx 26; Connexin 45; Connexin 26
 
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