Iodine alters gene expression in the MCF7 breast cancer cell line: evidence for an anti-estrogen effect of iodine.
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% I(2), 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.
Stoddard
Frederick R
FR
Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Brooks
Ari D
AD
Eskin
Bernard A
BA
Johannes
Gregg J
GJ
D015089:20-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007455:Iodine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
D004967:Estrogens; D012333:RNA, Messenger; D007455:Iodine; D015089:20-Hydroxysteroid Dehydrogenases; C115140:3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1