Location of Repository

Iodine Alters Gene Expression in the MCF7 Breast Cancer Cell Line: Evidence for an Anti-Estrogen Effect of Iodine

By Frederick R. Stoddard II, Ari D. Brooks, Bernard A. Eskin and Gregg J. Johannes

Abstract

The protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models. The molecular mechanisms responsible have not been identified but laboratory evidence suggests that iodine may inhibit cancer promotion through modulation of the estrogen pathway. To elucidate the role of iodine in breast cancer, the effect of Lugol's iodine solution (5% I2, 10% KI) on gene expression was analyzed in the estrogen responsive MCF-7 breast cancer cell line. Microarray analysis identified 29 genes that were up-regulated and 14 genes that were down-regulated in response to iodine/iodide treatment. The altered genes included several involved in hormone metabolism as well as genes involved in the regulation of cell cycle progression, growth and differentiation. Quantitative RT-PCR confirmed the array data demonstrating that iodine/iodide treatment increased the mRNA levels of several genes involved in estrogen metabolism (CYP1A1, CYP1B1, and AKR1C1) while decreasing the levels of the estrogen responsive genes TFF1 and WISP2. This report presents the results of the first gene array profiling of the response of a breast cancer cell line to iodine treatment. In addition to elucidating our understanding of the effects of iodine/iodide on breast cancer, this work suggests that iodine/iodide may be useful as an adjuvant therapy in the pharmacologic manipulation of the estrogen pathway in women with breast cancer

Topics: Research Paper
Publisher: Ivyspring International Publisher
OAI identifier: oai:pubmedcentral.nih.gov:2452979
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • http://creativecommons.org/lic... (external link)
  • Suggested articles

    Preview

    Citations

    1. (2005). Adverse effect of adjuvant tamoxifen in premenopausal breast cancer with cyclin D1 gene amplification. Cancer Res
    2. (2007). Amplification of CCND1 and PAK1 as predictors of recurrence and tamoxifen resistance in postmenopausal breast cancer. Oncogene
    3. (1992). An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase. FEBS Lett
    4. (2006). BRCA1 modulates xenobiotic stress-inducible gene expression by interacting with ARNT in human breast cancer cells.
    5. (1977). Breast atypia in altered iodine states: Intracellular changes. Senologia
    6. (2001). Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function. Blood
    7. (2005). Cyclin D1 antagonizes BRCA1 repression of estrogen receptor alpha activity. Cancer Res
    8. (2006). Cyclin D1 is necessary for tamoxifen-induced cell cycle progression in human breast cancer cells. Cancer Res
    9. (2004). Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients.
    10. (2005). Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett
    11. determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol
    12. (1976). Dietary iodine and cancer risk. Lancet
    13. (1995). Different tissue responses for iodine and iodide in rat thyroid and mammary glands. Biol Trace Elem Res
    14. (1997). Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase.
    15. (1979). Effect of iodide-deficiency on rat mammary gland. Virchows ArchB Cell PatholInclMolPathol
    16. (2005). ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes.
    17. (2003). Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr Relat Cancer
    18. (1996). Forssmann WG. hDIP--a potential transcriptional regulator related to murine TSC-22 and Drosophila shortsighted (shs)--is expressed in a large number of human tissues. Biochim Biophys Acta
    19. (2006). Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons.
    20. (2003). Functional expression of sodium iodide symporter (NIS) in human breast cancer tissue. Breast Cancer Res Treat
    21. (2002). GADD45 regulates G2/M arrest, DNA repair, and cell death in keratinocytes following ultraviolet exposure.
    22. (2005). Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage. Mutat Res
    23. (2005). Galectin-1 interacts with the {alpha}5{beta}1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p27.
    24. (2000). Glial cell line-derived neurotrophic factor (GDNF) is a proliferation factor for rat C6 glioma cells: evidence from antisense experiments. Antisense Nucleic Acid Drug Dev
    25. (1999). Incidence of breast carcinoma in women with thyroid carcinoma. Cancer
    26. (2006). Increased uptake of iodide by hormone-responsive compared to hormone-independent mammary tumors in GR mice.
    27. (2005). Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 prevents cancer promotion. MolCell Endocrinol
    28. (1993). Iodine replacement in fibrocystic disease of the breast.
    29. (1967). Mammary gland dysplasia in iodine deficiency. Studies in rats. Jama
    30. (2004). Notch signaling in mammary development and oncogenesis.
    31. (1996). O'Higgins NJ. A direct relationship between thyroid enlargement and breast cancer.
    32. (1989). Organization and expression of the cell cycle gene, ts11, that encodes asparagine synthetase. Mol Cell Biol
    33. (2002). Pribluda VS. 2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptors alpha and beta. Cancer Res
    34. (2003). purification, and characterization of human tyrosyl-tRNA synthetase. Protein Expr Purif
    35. (1975). Rat mammary gland atypia produced by iodine blockade with perchlorate. Cancer Res
    36. (2008). REDD1, a developmentally regulated transcriptional target of p63 and p53, links
    37. (2001). Regulation of the cell cycle by B-Myb. Blood Cells Mol Dis
    38. (2003). Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Carcinogenesis
    39. (1990). Structural and functional analysis of the human thymidylate synthase gene.
    40. (2003). Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone.
    41. (1996). Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat. J Surg Oncol
    42. (2004). The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia.
    43. (2006). The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA in the formation of depurinating adducts: implications for tumor-initiating activity. Chem Res Toxicol
    44. (2000). The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat Med
    45. (2000). The mammary gland iodide transporter is expressed during lactation and in breast cancer. NatMed
    46. (2002). Thymidine kinase in epithelial ovarian cancer: relationship with the other pyrimidine pathway enzymes.
    47. (1982). Thyroid disease and breast cancer: findings in a large case-control study.
    48. (2006). Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line. Endocr Relat Cancer

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.