Expression of gap junction genes connexin 32, connexin 43 and their proteins in hepatocellular carcinoma and normal liver tissues

Abstract

AIM To investigate the significance and mechanism of cx-32 mRNA, cx-43 mRNA and their proteins in hepatocarcinogenesis. METHODS Sixty-one cases of HCC and 14 cases of normal liver tissues were detected by immunohistochemical and in situ hybridization (ISH) methods. RESULTS In HCC grades I, II, III and normal liver tissues, the positive rates of Cx32 protein were 55.6%, 42.1%, 18.2% and 92.9%, respectively. The detection rates of Cx43 protein were 44%, 26.3%, 12.1% and 78.6%, respectively. There was significant difference in Cx32 and Cx43 protein between HCC and normal liver tissues (P<0.01). ISH the positive rates of cx 32 mRNA shown by ISH in HCC grades I, II, III and normal liver tissues were 88.9%, 84.2%, 87.9% and 92.9%, respectively. Those of cx43 mRNA were 77.8%, 78.6%, 78. 8% and 85.7%, respectively. There was no statistical difference in the positive rates of cx32 mRNA and cx43 mRNA between HCC and normal liver tissue (P>0.05). CONCLUSION The aberrant location of Cx32 and Cx43 proteins could be responsible for progression of hepatocarcinogenesis, and the defect of cx genes in post-translational processing might be the possible mechanism.

Modifications in Connexin Expression in Liver Development and Cancer

“…In addition, in cultures of primary hepatocytes, which are inherently prone to alterations in the differentiation status and thus can serve as an experimental model to study this condition, inhibitors of histone deacetylases, constituting another critical determinant of the epigenome, have been demonstrated to affect connexin expression and GJIC in favour of the differentiated status (Vinken et al, 2006c(Vinken et al, , 2007. Another hallmark of tumour cells includes aberrant connexin localisation (Leithe et al, 2006;Ma et al, 2000Ma et al, , 2002Ma et al, , 2003Mesnil et al, 2005). Thus, Cx32 typically accumulates in the cytoplasm of cancerous human hepatocytes, both in vitro and in vivo (Kawasaki et al, 2011;Li et al, 2007).…”

Connexin 43 transfection in basaloid squamous cell carcinoma cells

“…Disruption of connexins has been frequently reported in malignant tumor cells such as hepatocellular carcinoma (5) and breast carcinoma (6), and in carcinogenesis of the cervix (7) and endometrium (8). Saitoh et al demonstrated changes in the expression of Cx26 and 43 in hamster tongue epithelium during wound healing and carcinogenesis (9).…”

Participação das conexinas 43 e 32 no desenvolvimento da fibrose hepática: estudo em camundongos geneticamente modificados

“…Diversos estudos relacionados à carcinogênese também demonstraram redução das conexinas, indicando-as como genes supressores de tumores e de grande relevância nos eventos de transformação celular (TEMME et al, 1997;OMORI et al, 2001;MA et al, 2000MA et al, , 2002EVERT et al, 2002).…”

“…No entanto, esta correlação nem sempre se mostra fidedigna em todos os tipos celulares (KARDAMI et al, 2007) ou nos diferentes processos patológicos (DAGLI; HERNANDEZ-BLAZQUEZ, 2007). Alguns estudos realizados em animais com deficiência de Cx32 demonstraram maior susceptibilidade destes animais ao desenvolvimento de tumores hepáticos (TEMME et al, 1997;MA et al, 2000MA et al, , 2002OMORI et al, 2001;EVERT et al, 2002). No entanto, estes mesmos animais submetidos ao modelo da hepatectomia parcial apresentaram menor proliferação celular dos hepatócitos (TEMME et al, 2000).…”