Tamoxifen Induces Expression of Immune Response-Related Genes in Cultured Normal Human Mammary Epithelial Cells

Details

• Personal Author:
  Divi RL ; Leil TA ; Olivero OA ; Poirier MC ; Schild-Hay LJ ; Weston A
• Description:
  Use of tamoxifen is associated with a 50% reduction in breast cancer incidence and an increase in endometrial cancer incidence. Here, we documented tamoxifen-induced gene expression changes in cultured normal human mammary epithelial cells (strains 5, 16, and 40), established from tissue taken at reduction mammoplasty from three individuals. Cells exposed to 0, 10, or 50 mu mol/L of tamoxifen for 48 hours were evaluated for (E)-alpha-(deoxyguanosine-N-2-yl)-tamoxifen (dG-N-2-TAM) adduct formation using TAM-DNA (DNA modified with dG-N2-TAM) chemiluminescence immunoassay, gene expression changes using National Cancer Institute DNA-oligonucleotide microarray, and real-time PCR. At 48 hours, cells exposed to 10 and 50 mu mol/L of tamoxifen were 85.6% and 48.4% viable, respectively, and there were no measurable dG-N-2-TAM adducts. For microarrays, cells were exposed to 10 mu mol/L of tamoxifen and genes with expression changes of >3-fold were as follows: 13 genes up-regulated and 1 down-regulated for strain 16; 17 genes up-regulated for strain 5, and 11 genes up-regulated for strain 40. Interferon-inducible genes (IFITM1, IFIT1, MXI, and GIP3), and a potassium ion channel (KCNJ1) were up-regulated in all three strains. No significant expression changes were found for genes related to estrogen or xenobiotic metabolism. Real-time PCR revealed the upregulation of IFNA1 and confirmed the tamoxifen-induced upregulation of the five other genes identified by microarray, with the exception of GIP3 and MX1, which were not upregulated in strain 40. Induction of IFN-related genes in the three normal human mammary epithelial cell strains suggests that, in addition to hormonal effects, tamoxifen exposure may enhance immune response in normal breast tissue. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Genetics Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Microarray Breast-cancer Cancer-rates Cell-biology Cell-cultures Cell-growth Cell-morphology Genes Genetic-factors IFN RT-PCR TAM-DNA Chemiluminescence Immunoassay

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• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; New Jersey ; OSHA Region 2 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  69
• Issue:
  3
• NIOSHTIC Number:
  nn:20035047
• Citation:
  Cancer Res 2009 Feb; 69(3):1150-1155
• Contact Point Address:
  Miriam C. Poirier, Carcinogen-DNA Interactions Section, CCR, LCBG, National Cancer Institute, NIH, Building 37 Room 4032, MSC-4255, 37 Convent Drive, Bethesda, MD 20892-4255
• Email:
  poirierm@exchange.nih.gov
• Federal Fiscal Year:
  2009
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2e85731373f16069761caba179b7cb944c86791cb0b3e9feda371ef6587861770ff2cfe58573592a150c5478934cd24e025e746194f62df40d6bf691a934a074
• Download URL:
  https://stacks.cdc.gov/view/cdc/187033/cdc_187033_DS1.pdf
• File Type:
  [PDF - 241.57 KB ]