Modulation of the connexin26 tumor suppressor gene expression through methylation in human mammary epithelial cell lines.
Modulation of the connexin26 tumor suppressor gene expression through methylation in human mammary epithelial cell lines.
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DOI：
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发表时间：
2000
影响因子：
2
通讯作者：
R. Singal;Z. Tu;J. Vanwert;G. Ginder;D. Kiang
中科院分区：
文献类型：
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作者：
R. Singal;Z. Tu;J. Vanwert;G. Ginder;D. Kiang
正常乳腺上皮细胞主要表达间隙连接蛋白26（Cx 26），其在乳腺癌中减少或缺失。由于连接蛋白基因突变是罕见的，我们研究了Cx 26基因抑制是否与高甲基化有关。材料与方法检测了五种乳腺上皮细胞系的Cx 26 mRNA表达和高甲基化。用DNA甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷（5-Aza-CdR）处理，以确定Cx 26基因表达是否可以上调。结果Cx 26在永生化人乳腺上皮细胞系（MCF-10）中的表达很容易检测到，而在乳腺癌细胞系（MCF-7，BT-20，T47-D）中的表达明显减少（MDA-MB 231）或检测不到。在MCF-10和MCF-7细胞中观察到Cx 26 5'区的高甲基化。用5-Aza-CdR处理导致乳腺癌细胞系中Cx 26表达的轻微诱导或不诱导。结论Cx 26基因的高甲基化可能是人乳腺癌细胞系中Cx 26基因抑制的主要机制。
BACKGROUND Normal mammary epithelial cells express mainly gap junction connexin 26 (Cx26) that is either reduced or absent in breast cancers. Since connexin gene mutations are rare we examined if Cx26 gene repression is related to hypermethylation. MATERIALS AND METHODS Five breast epithelial cell lines were examined for Cx26 mRNA expression and hypermethylation. Treatment with a DNA methyltransferase inhibitor, 5-Aza-2'-deoxycytidine (5-Aza-CdR), was carried out to determine if Cx26 gene expression could be upregulated. RESULTS Cx26 expression was easily detectable in an immortalized human mammary epithelial cell line (MCF-10) and markedly diminished (MDA-MB231) or undetectable in (MCF-7, BT-20, T47-D) breast cancer cell lines. Hypermethylation of the Cx26 5' region was observed in MCF-10 and MCF-7 cells. Treatment with 5-Aza-CdR resulted in slight or no induction in Cx26 expression in breast cancer cell lines. CONCLUSIONS Hypermethylation is unlikely to be a major mechanism for Cx26 gene repression in human mammary cancer cell lines.