Journal Article

Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer

Lor-wai Tan, Tina Bianco and Alexander Dobrovic

in Carcinogenesis

Volume 23, issue 2, pages 231-236
Published in print February 2002 | ISSN: 0143-3334
Published online February 2002 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/23.2.231
Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer

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Intercellular communication via gap junctions is a mechanism for tumor suppression. Connexin 26 (Cx26) is a structural component of gap junctions expressed by breast epithelial cells. Expression levels of Cx26 are reduced in many breast tumors. Methylation-sensitive single-stranded conformation analysis showed variable methylation in the promoter region CpG island in 11 out of 20 (55%) breast cancer patients. Heterogeneity in methylation patterns was observed both between and within tumors. The degree of methylation ranged from a few CpG dinucleotides to almost all the CpG dinucleotides in the analyzed region. The most frequently methylated CpG was in an Sp1 site known to be important for Cx26 gene expression. One of eight breast cancer cell lines (MD-MBA-453) was methylated in the promoter region and did not express Cx26. Treatment of MDA-MB-453 with 5-aza-2′-deoxycytidine resulted in the re-expression of Cx26 mRNA. Methylation of the promoter region is likely to be an important mechanism in modulating the expression of Cx26 in breast cancer.

Keywords: Cx26, Connexin 26; MS-SSCA, methylation-specific single-stranded conformational analysis; RT–PCR, reverse transcription polymerase chain reaction.

Journal Article.  4158 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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