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Tamoxifen induces expression of immune response-related genes in cultured normal human mammary epithelial cells.

Authors
Schild-Hay-LJ; Leil-TA; Divi-RL; Olivero-OA; Weston-A; Poirier-MC
Source
Cancer Res 2009 Feb; 69(3):1150-1155
NIOSHTIC No.
20035047
Abstract
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.
Keywords
Genes; Genetic-factors; Cancer-rates; Cell-biology; Cell-cultures; Cell-growth; Cell-morphology; Genetic-factors; Breast-cancer; Cancer-rates; Author Keywords: Microarray; RT-PCR; TAM-DNA chemiluminescence immunoassay; IFN
Contact
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
CODEN
CNREA8
Publication Date
20090201
Document Type
Journal Article
Email Address
poirierm@exchange.nih.gov
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0008-5472
NIOSH Division
DRDS
Source Name
Cancer Research
State
WV; MD; NJ
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