Cell proliferation and advancement of hepatocarcinogenesis in the rat are associated with a decrease in connexin 32 expression

Tsuda, Hiroyuki; Asamoto, Makoto; Baba, Hiroyasu; Iwahori, Yoshio; Matsumoto, Kazuyuki; Iwase, Teruhiko; Nishida, Yoshihisa; Nagao, Shizuko; Hakoi, Kazuo; Yamaguchi, Shuji; Ozaki, Keisuke; Yamasaki, Hiroshi

doi:10.1093/carcin/16.1.101

Cited by 41 publications

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“…In addition, the selective communication of molecules through gap junctions may inhibit some cellular activities, i.e. proliferation (Loewenstein & Rose 1992, Tsuda et al 1995, Shah & Murray 2001, and thus direct cellular activities toward those metabolic pathways used in steroidogenesis and/or cellular differentiation. It appears that the cells of the inner zones have a greater capacity for, and presumably a greater functional dependence on, intercellular communication than cells of the zona glomerulosa.…”

Section: Discussionmentioning

confidence: 99%

Gap junction proteins and cell-cell communication in the three functional zones of the adrenal gland

Davis

Prentice

Murray

2002

Journal of Endocrinology

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Mouse and monkey adrenal glands were used to study the relationships between gap junction protein expression, intercellular communication and adrenal zonation. Dye communication patterns were determined by incubating freshly excised and hemisected adrenal glands in Lucifer yellow, a gap junction permeable fluorescent dye. Immunohistochemical techniques were used to localize adrenal gap junction proteins. The combination of these two techniques permitted the correlation of gap junction proteins with dye transfer and hormone responses in specialized regions of the adrenal cortex. Lucifer yellow dye communication was most pronounced in the inner glucocorticoid/androgen-producing regions (zona fasciculata/zona reticularis), but was virtually absent in the outer mainly mineralocorticoid-producing region (zona glomerulosa). This pattern of dye communication was coincident with immunohistochemical localization of the gap junction protein, 1 Cx43. The variations in communication and 1 Cx43 expression within the adrenal cortex are thought to be relevant to normal physiological regulation of the adrenal gland.

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Section: Discussionmentioning

confidence: 99%

Gap junction proteins and cell-cell communication in the three functional zones of the adrenal gland

Davis

Prentice

Murray

2002

Journal of Endocrinology

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“…A recent study indicates that Cx32 expression apparently correlates with cellular independence and growth advantage during tumor progression in the liver (14). Chronic administration of PB, while maintaining a decreased level of Cx32 protein, resulted in no increase in DNA synthesis, suggesting that PB produces no effect on Cx32 expression by DNA through such synthesis (9).…”

Section: Discussio~mentioning

confidence: 99%

Effect of Phenobarbital on Hepatic Gap Junctional Intercellular Communication in Rats

et al. 1998

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The effects of in v i w exposure to phenobarbital (PB) on hepatic gap junctional intercellular communication (GJIC) and conncxin protein expression in Sprague-Dawley rats were examined by in vivolirn virro dye-transfer assay, immunohistochemical staining, and by Western blot analysis. PB (50 mgkg) was administered orally once a day for up to 6 wk. The average size of the dye spread after injection of Lucifer Yellow decreased at week 1 and remained at the same level until \veek 6. The area and number of connexin 32 (Cx32) spots pcr hcpatocyte in the central zone of liver lobules decreased from week 1 to week 6, but no change of Cx32 spots in thc pcriphcral zone was obscrvcd. Thc average area and number of connexin 26 (Cx26) spots per hepatocytes showed no clear change through thc cxpcrimcntal pcriods. Thc dccrcascd level of Cx32 protein in plasma membranes was observed in the PB group. These results suggest that PB, a liver tumor-promoting agent, inhibits hepatic GJIC in vivo in rats and that aberrant Cx32 protein expression and/or localization may be responsible for this effect.Kejwords. Liver; gap junction; connexin; tumor promoter INTRODUCTION Gap junctional intercellular communication (GJIC) is considered to play an important role in carcinogenesis. A recent review of the ability of chemicals with tumor-promoting or tumor-inhibiting activity to modulate GJIC reports that more than 100 substances have been shown to inhibit GJIC (1). The inhibition of GJIC appears to be the most common property of chemicals with tumor-promoting activity; however, phenobarbital (PB), a liver tumor promoter (2, lo), has shown mixed results (negative andlor positive) in iit vitro assays (1). It was reported that PB (0.05% in diet) diminished the total area and size of rat hepatocyte gap junctions by freeze-fracture analysis in vivo (12). The level of gap junction protein mRNA in rat liver was observed to be markedly reduced at 4 and 11 wk of PB exposure (0.1% in drinking water) (7). However, there have been few studies that examine the hepatic gap junctional functions of rats exposed to PB iii vivo (5). We have studied the effect of DDT on hepatic GJIC in rats and clearly demonstrated that DDT inhibited hepatic GJIC and caused aberrant connexin 32 (Cx32) and connexin 26 (Cx26) protein expression iii vivo (13). This study was conducted to demonstrate the inhibition of hepatic GJIC in rats exposed to PB-iiz vivo and compare these results with the effects of DDT In the present study, the effects of PB on hepatic GJIC of rats treated orally with PB (50 mglkgiday) for up to 6 wk were examined by iit vivoiiit vitro dye-transfer assay using freshly removed liver slices. Localization of the hepatic gap junction proteins, Cx32 and Cx26, and protein levels of

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“…Because there was no decrease in levels of cx32 mRNA and cx43 mRNA in HCC and normal liver tissues, the aberrant localization of Cx32 and Cx43 might be responsible for the reduced GJIC in HCC [6] . It appears that the control mechanisms of cx32 and cx43 genes transcription are not affected during human liver tumorigenesis.…”

Section: Discussionmentioning

confidence: 91%

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

Dong¹

2000

WJG

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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.

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Cell proliferation and advancement of hepatocarcinogenesis in the rat are associated with a decrease in connexin 32 expression

Cited by 41 publications

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Gap junction proteins and cell-cell communication in the three functional zones of the adrenal gland

Gap junction proteins and cell-cell communication in the three functional zones of the adrenal gland

Effect of Phenobarbital on Hepatic Gap Junctional Intercellular Communication in Rats

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

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