Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

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  • Haakensen, Vilde D
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  • Bjøro, Trine
    • Other Affiliation: Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Deptartment of Medical Biochemistry and Institute of Clinical Biochemistry, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  • Lüders, Torben
    • Other Affiliation: Department of Clinical Molecular Biology, Division of Medicine and Laboratory Sciences, Institute for Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway
  • Riis, Margit
    • Other Affiliation: Department of Clinical Molecular Biology, Division of Medicine and Laboratory Sciences, Institute for Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway; Department of Surgery, Akerhus University Hospital, Lørenskog, Norway
  • Bukholm, Ida K
    • Other Affiliation: Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Surgery, Akerhus University Hospital, Lørenskog, Norway
  • Kristensen, Vessela N
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology, Division of Medicine and Laboratory Sciences, Institute for Clinical Medicine, Akershus University Hospital, University of Oslo, Lørenskog, Norway
  • Troester, Melissa
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Gillings School of Global Public Health, Department of Epidemiology
  • Homen, Marit M
    • Other Affiliation: Department of Radiology, University Hospital of North Norway, Tromsø, Norway
  • Ursin, Giske
    • Other Affiliation: Department of Nutrition, School of Medicine, University of Oslo, Oslo, Norway; Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, USA; Cancer Registry of Norway, Oslo, Norway
  • Børresen-Dale, Anne-Lise
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  • Helland, Åslaug
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway
Abstract
  • Abstract Background High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. Methods We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Results Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. Conclusions We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the local production of estradiol. This is the first report studying such associations in normal breast tissue in humans.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Vilde D Haakensen et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Cancer
Journal volume
  • 11
Journal issue
  • 1
Page start
  • 332
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2407
Bibliographic citation
  • BMC Cancer. 2011 Aug 03;11(1):332
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 15, 2016

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