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Dysregulation of MicroRNAs is Associated with Expression of a Hypermethylation Defect in Primary Basal‐like Breast Cancer
Author(s) -
Sandhu Rupninder,
Coleman William B
Publication year - 2011
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.25.1_supplement.122.1
Subject(s) - dnmt3b , basal (medicine) , breast cancer , dna methylation , gene silencing , microrna , methylation , cancer research , biology , cancer , gene expression , oncology , pathology , medicine , gene , endocrinology , genetics , insulin
Basal‐like breast cancers frequently express a hypermethylation defect associated with DNMT hyperactivity, DNMT3b overexpression, and concurrent silencing of numerous genes. Examination of methylation‐sensitive gene expression in 33 primary breast cancers showed that 10/16 (63%) basal‐like tumors express the hypermethylation defect, whereas only 3/17 (17%) non‐basal‐like tumors express this defect. We examined the expression of microRNAs (miRs) that regulate DNMT3b (miR‐26a, 26b, 29a, 29b, 29c, 148a, 148b, 203) by qPCR (normalized to RNU66) in 70 primary breast cancers (36 luminal A, 13 luminal B, 5 Her2+, 16 basal‐like) and 18 normal mammoplasty tissues to determine the mechanism governing DNMT3b overexpression in the hypermethylation defect. Significantly reduced expression of 29c distinguished basal‐like cancers from other subtypes. miR expression patterns revealed two groups among the basal‐like breast cancers corresponding to diminished expression (n=10) and normal levels of expression (n=6). These results suggest strongly that (i) reduced expression of 29c is characteristic of basal‐like breast cancers, (ii) two subgroups of basal‐like breast cancers can be identified based on miR expression and methylation‐sensitive gene expression, and (iii) the subgroup of basal‐like breast cancers with reduced expression of multiple regulatory miRs express the hypermethylation defect.