Down-Regulation of Connexin 32 Gene Expression through DNA Methylation in a Human Renal Cell Carcinoma Cell

Hirai, Ayako; Yano, Tomohiro; Nishikawa, Kazuhiro; Suzuki, Kazuyuki; Asano, Ryuji; Satoh, Haruna; Hagiwara, Kiyokazu; Yamasaki, Hiroshi

doi:10.1159/000070653

Cited by 34 publications

(29 citation statements)

References 13 publications

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“…13 Hypermethylation in the promoter region is a mechanism for the Cx32 gene repression in human renal cell carcinoma cells. 22,23 Cx26 is a structural component of gap junctions expressed in breast epithelial cells. Expression levels of Cx26 are reduced in many breast tumors.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

et al. 2007

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Summary Down-regulation of Cx43 expression had been shown to occur in nasopharyngeal carcinoma cells. The present study was undertaken to estimate if methylation of the promoter region in Cx43 gene was responsible for the repression of Cx43 expression in the CNE-1 nasopharyngeal carcinoma cells. Calcein transfer and lucifer yellow transfer were detected to evaluate gap junction intercellular communication (GJIC) in CNE-1 cells. It was found that the control CNE-1 cells showed no fluorescent dye transfer. After treatment with DNA methyltransferase inhibitor 5-aza-CdR, fluorescent dye transfer between cells became obvious. RT-PCR and Western blot were performed to determine the expression of Cx43 gene. The control CNE-1 cells showed a low expression level of Cx43, whereas 5-aza-CdR-treated CNE-1 cells showed an enhanced level of Cx43 expression. Methylation-sensitive restriction enzyme and PCR analysis showed that the methylation of the Cx43 gene promoter region occurred in CNE-1 cells. In addition, treatment with 5-aza-CdR inhibited the growth (including anchorage-independent growth) of CNE-1 cells, and resulted in an accumulation of cells in G0/G1 phase. These results indicate the promoter methylation as an important role in inactivation of Cx43 in CNE-1 cells.

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Section: Discussionmentioning

confidence: 99%

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

et al. 2007

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“…For example, in our previous study, preneoplastic and neoplastic lesions such as endometrial hyperplasia and carcinoma showed obvious decreases in levels of Cx26 and Cx32 mRNA, and immunohistochemically aberrant localization . Recently, several studies demonstrated that hypermethylation in the promoter region was a mechanism for the Cx32 gene repression (Singal et al, 2000;Tan et al, 2002;Hirai et al, 2003), although it was not found in other tumors (Loncarek et al, 2003). However, little is known about the mechanism decreasing GJIC in the endometrium.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of estrogen receptor-α gene suppresses gap junctional intercellular communication in endometrial carcinoma cells

et al. 2004

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Stimulation of the endometrium by estrogens without the differentiating effect of progestins is the primary etiological factor associated with the development of endometrial hyperplasia and adenocarcinoma. However, the correlation between sex steroids and gap junctional intercellular communication (GJIC), which is considered to play an important role in the control of cell growth and differentiation, is not well known in endometrial carcinoma. In this study, we focused on the influence of estrogen and its receptor in connexin (Cx) expression and GJIC in endometrial carcinoma cells, established stable clone IK-ER1 overexpressing ER-a to transfect the expression vector and analysed them in various hormonal conditions. The growth of IK-ER1 was accelerated by 17b-estradiol and the acceleration of the 5-bromo-25-deoxyuridine labeling index was observed. GJIC was assayed by scoring the number of dye-coupled cells after microinjecton of single cells with Lucifer-Yellow, and subcellular localization of Cx26 and Cx32 was analysed by immunocytochemistry. In the presence of estradiol, dyecoupled cells of IK-ER1 were significantly reduced compared to those without estradiol and the reduction was completely inhibited by adding ICI182.780, a pure antiestrogen substrate. Cxs were detected as only small spots by immunocytochemistry, and Western blotting showed that the expression was decreased. These results suggest that activation of ER-a by estrogen results in tumor progression by stimulating cell growth and suppressing GJIC via suppression of the expression of Cxs in endometrial carcinogenesis.

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“…Indeed, inactivation of the Cx26, Cx32 and Cx43 genes by hypermethylation of their promoter regions has been demonstrated. [162][163][164][165] Epigenetic effect of toxicants has been well documented for hepatic Cx43, 33,139 and could occur in the testis. This epigenetic effect could also be operative, during critical male programming windows of testis development, and lead to transgenerational reproductive dysfunction.…”

Section: Effects Of Environmental Toxicants On Connexin 43 In the Devmentioning

confidence: 99%

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

et al. 2011

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Down-Regulation of Connexin 32 Gene Expression through DNA Methylation in a Human Renal Cell Carcinoma Cell

Cited by 34 publications

References 13 publications

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation

Overexpression of estrogen receptor-α gene suppresses gap junctional intercellular communication in endometrial carcinoma cells

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

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