Show simple item record

dc.contributor.authorStraume, Anne Hegeen_US
dc.contributor.authorKnappskog, Stianen_US
dc.contributor.authorLønning, Per Eysteinen_US
dc.description.abstractBreast cancers reveal elevated E2 levels compared to plasma and normal breast tissue. Previously, we reported intra-tumour E2 to be negatively correlated to transcription levels of 17β-HSD2 but positively correlated to 17β-HSD7. Here, we explored these mechanisms further by analysing the same breast tumours for 17β-HSD2 and -7 SNPs, as well as 17β-HSD7 gene copy number. Among the SNPs detected, we found the 17β-HSD2 rs4445895_T allele to be associated with lower intra-tumour mRNA (p = 0.039) and an elevated intra-tumour E2 level (p = 0.006). In contrast, we found the 17β-HSD7 rs1704754_C allele to be associated with elevated mRNA (p = 0.050) but not to E2 levels in breast tumour tissue. Surprisingly, 17β-HSD7 – gene copy number was elevated in 19 out of 46 breast tumours examined. Elevated copy number was associated with an increased mRNA expression level (p = 0.013) and elevated tumour E2 (p = 0.025). Interestingly, elevated 17β-HSD7 – gene copy number was associated with increased expression not only of 17β-HSD7, but the 17β-HSD7_II pseudogene as well (p = 0.019). Expression level of 17β-HSD7 and its pseudogene was significantly correlated both in tumour tissue (rs = 0.457, p = 0.001) and in normal tissue (rs = 0.453, p = 0.002). While in vitro transfection experiments revealed no direct impact of 17β-HSD7 expression on pseudogene level, the fact that 17β-HSD7 and 17β-HSD7_II share a 95.6% sequence identity suggests the two transcripts may be subject to common regulatory mechanisms. In conclusion, genetic variants of 17β-HSD2 and 17β-HSD7 may affect intra-tumour gene expression as well as breast cancer E2 levels in postmenopausal women.en_US
dc.rightsAttribution-NonCommercial-NoDerivs CC BY-NC-NDeng
dc.subjectGene expressioneng
dc.subjectSingle nucleotide polymorphismseng
dc.subjectBreast cancereng
dc.subjectPostmenopausal oestrogen synthesiseng
dc.titleEffects of SNP variants in the 17β-HSD2 and 17β-HSD7 genes and 17β-HSD7 copy number on gene transcript and estradiol levels in breast cancer tissueen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2014 The Authors
dc.source.journalJournal of Steroid Biochemistry and Molecular Biology
dc.subject.nsiVDP::Medical sciences: 700::Clinical medical sciences: 750::Oncology: 762eng
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Onkologi: 762nob

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs CC BY-NC-ND
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs CC BY-NC-ND