dc.contributor.author | Straume, Anne Hege | en_US |
dc.contributor.author | Knappskog, Stian | en_US |
dc.contributor.author | Lønning, Per Eystein | en_US |
dc.date.accessioned | 2014-12-05T08:15:05Z | en_US |
dc.date.accessioned | 2014-12-05T11:00:44Z | en_US |
dc.date.accessioned | 2014-12-09T15:43:59Z | |
dc.date.available | 2014-12-09T15:43:59Z | |
dc.date.issued | 2014-02-18 | eng |
dc.identifier.issn | 0960-0760 | |
dc.identifier.uri | https://hdl.handle.net/1956/8864 | |
dc.description.abstract | Breast 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.language.iso | eng | eng |
dc.publisher | Elsevier | eng |
dc.rights | Attribution-NonCommercial-NoDerivs CC BY-NC-ND | eng |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | eng |
dc.subject | 17β-HSD2 | eng |
dc.subject | 17β-HSD7 | eng |
dc.subject | Gene expression | eng |
dc.subject | Single nucleotide polymorphisms | eng |
dc.subject | Breast cancer | eng |
dc.subject | Postmenopausal oestrogen synthesis | eng |
dc.title | Effects 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 tissue | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2014-12-05T08:15:06Z | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2014 The Authors | |
dc.identifier.doi | https://doi.org/10.1016/j.jsbmb.2014.02.003 | |
dc.identifier.cristin | 1153080 | |
dc.source.journal | Journal of Steroid Biochemistry and Molecular Biology | |
dc.source.40 | 143 | |
dc.source.pagenumber | 192-198 | |
dc.subject.nsi | VDP::Medical sciences: 700::Clinical medical sciences: 750::Oncology: 762 | eng |
dc.subject.nsi | VDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 | nob |