Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

Nakashima, Yuichi; Ono, Takashi; Yamanoi, Akira; El-Assal, Osama N.; Kohno, Hitoshi; Nagasue, Naofumi

doi:10.1007/s00535-003-1386-2

Cited by 64 publications

(62 citation statements)

References 23 publications

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“…Since both liver development and cancer are associated with clear-cut changes in connexin expression, these proteins may form a novel set of clinical diagnostic indicators and therapeutic targets (Nakashima et al, 2004;Nakata et al, 1996;Yamaoka et al, 2000). Specifi cally, connexins could be used as biomarkers of disease.…”

Section: Discussionmentioning

confidence: 99%

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Modifications in Connexin Expression in Liver Development and Cancer

Vinken

Kock

Oliveira

et al. 2012

Cell Communication & Adhesion

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The establishment of an elaborate gap junctional intercellular communication network, especially between hepatocytes, is important for normal liver development. In fact, the production of the gap junction building blocks, the connexins, undergoes several well-defi ned changes throughout the hepatic differentiation process. This ultimately results in the acquisition of an adult connexin expression pattern which is critical for maintaining the fully differentiated hepatocyte-specifi c phenotype. Abnormalities of connexin production are observed in a number of pathological conditions, such as during liver cancer. This article provides an overview of these processes with emphasis on the underlying molecular mechanisms.

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Section: Discussionmentioning

confidence: 99%

“…hepatitis, fi brosis and cirrhosis) as well as during hepatotoxicity (Nakashima et al, 2004;Nakata et al, 1996;Yamaoka et al, 2000). This is equally refl ected at the posttranscriptional level and is caused by increased degradation of Cx32 mRNA molecules (Gingalewski et al, 1996).…”

Section: Connexins and Alterations In The Liver Differentiation Statusmentioning

confidence: 99%

Modifications in Connexin Expression in Liver Development and Cancer

Vinken

Kock

Oliveira

et al. 2012

Cell Communication & Adhesion

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“…Cxs have been previously reported in various types of malignant tumors, including breast, liver, colon, and esophageal tumors [5][6][7][8][9][10]. A decrease or loss of Cxs expression has also been reported [6,11].…”

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confidence: 90%

“…In addition, Conklin et al [6] reported that Cx43 is downregulated at various stages of breast cancer progression, including ductal carcinomas in situ, infiltrating ductal carcinoma and infiltrating lobular carcinomas. Although some reports have implicated reduced or absent Cx expression in cancer progression, others have suggested that altered subcellular localization of Cx32, specifically, intracytoplasmic expression, is involved [7][8][9]. Generally Cx is distributed primarily along membranes of normal cells, but in hepatocellular carcinoma Cx32 is mostly detected in both the cytoplasm and on the cell membranes of tumor cells [7].…”

mentioning

confidence: 99%

“…Although some reports have implicated reduced or absent Cx expression in cancer progression, others have suggested that altered subcellular localization of Cx32, specifically, intracytoplasmic expression, is involved [7][8][9]. Generally Cx is distributed primarily along membranes of normal cells, but in hepatocellular carcinoma Cx32 is mostly detected in both the cytoplasm and on the cell membranes of tumor cells [7]. In colorectal cancers, Cx26-positive adenocarcinoma cells exhibit primarily cytoplasmic Cx26 [8,9].…”

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Altered Expression and Localization of Connexin32 in Human and Murine Gastric Carcinogenesis

et al. 2010

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Background Intercellular communication via gap junctions, composed of protein subunits called connexins (Cxs), plays a key role in controlling cell growth, differentiation and carcinogenesis. Impaired gap junctional intercellular communication has been reported in various cancers and diseases. Aims We investigated Cx32 expression patterns and semiquantitatively assessed Cx32 expression in cancers and preneoplastic lesions. To determine if cell proliferation is correlated with Cx32 expression, we evaluated Ki67 expression in a gastric cancer mouse model. Methods In human and mouse, normal stomach and gastric adenocarcinoma tissues were used for immunohistochemical analyses.Results Cx32 was detected at cell-cell (intercellular) contact points in normal cells and exhibited punctate intercellular and intracytoplasmic staining in cancer cells. The frequency of Cx32 loss of expression was significantly higher in human adenocarcinomas than in normal stomach. As tumor cells were less differentiated, Cx32 expression levels and intercellular and intracytoplasmic staining were also significantly lower. The Cx32 expression pattern in the mouse gastric cancer model was similar in several important respects to that of human. In mucous metaplasia of the mouse stomach, Cx32 was mainly expressed in the cytoplasm of epithelial cells. There was also an inverse correlation between Cx32 expression and cell proliferation in mouse tumors. However, there was no difference in the levels of Cx32 mRNA between normal and cancerous tissues. Conclusions These findings suggest that altered Cx32 expression, a loss of intercellular Cx32 and a gain of intracytoplasmic Cx32 in the form of punctate ''dot'', plays an important role in the formation of gastric adenocarcinomas.

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