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Dysregulation of MicroRNAs that Regulate DNMT3b Expression in Primary Breast Cancers
Author(s) -
Sandhu Rupninder,
Coleman William B
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.925.3
Subject(s) - breast cancer , microrna , gene silencing , dna methylation , dnmt3b , cancer research , methylation , biology , cancer , gene expression , oncology , pathology , medicine , gene , genetics
A subset of breast cancer cell lines express a hypermethylation defect related to DNMT3b overexpression resulting from loss of expression of regulatory microRNAs (miRs). Most primary breast cancers overexpress DNMT3b compared to normal breast epithelia, and certain subsets of breast cancer (basal‐type) display gene expression signatures that reflect methylation‐dependent silencing of multiple genes, consistent with the expression of a hypermethylation defect in vivo . Several miRs have been implicated in the regulation of DNMT3b. We examined the expression of miRs‐29a, 29b, 29c, 148a, and 148b, in a group of 15 primary breast cancers (n=6 luminal A, n=2 luminal B, n=2 Her2+, n=5 basal) and two normal breast tissues. miR expression levels <50% of normal were found in 9/15 (60%) tumors for 29a/29c, 10/15 (67%) tumors for 29b, 12/15 (80%) tumors for 148a, and 8/15 (53%) for 148b. Further, 12/15 (80%) tumors lost expression =2 miRs, 9/15 (60%) lost =3 miRs, and 8/15 (53%) lost =4 miRs. The aggregate miR expression score did not differ for luminal A versus basal breast cancers, suggesting that loss of additional factors may govern the hypermethylation defect. These results suggest that loss of expression of miRs‐29a, 29b, 29c, 148a, and 148b occurs commonly among primary breast cancers, but may contribute to the expression of a hypermethylation defect in a subset of these neoplasms. Support: NIH CA 78343