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  • Title: Inhibition of endometrial carcinoma cell growth using antisense estrogen receptor oligodeoxyribonucleotides.
    Author: Taylor AH, al-Azzawi F, Pringle JH, Bell SC.
    Journal: Anticancer Res; 2002; 22(6C):3993-4003. PubMed ID: 12553024.
    Abstract:
    BACKGROUND: The sex hormone 17 beta-estradiol acts as a mitogen in a number of tissues, including the endometrium, through direct interaction with the estrogen receptor (ER alpha). In the protection of the female breast and endometrium from cancer progression it would be advantageous to inhibit estrogenic action, therefore many estrogen receptor antagonists have been made. However, the most clinically relevant anti-estrogens for breast cancer have a detrimental effect on the endometrium and induce or exacerbate existing endometrial oncogenesis. Specific anti-estrogenic potential that is directed against the endometrial ER alpha theoretically could be achieved using antisense oligodeoxyribonucleotide transfection techniques. MATERIALS AND METHODS: To discover the most effective antisense oligodeoxyribonucleotides against the human ER alpha, a series of oligodeoxyribonucleotides were synthesised and tested in a human endometrial cancer cell line that expresses a functional ER alpha. RESULTS: Transfection with antisense oligodeoxyribonucleotides, directed against different regions of the human ER alpha, significantly inhibited ER alpha protein production without affecting ER beta protein levels. Antisense oligodeoxyribonucleotides directed against the translational start site demonstrated reduced binding of radiolabeled 17 beta-estradiol and a complete inhibition of estrogen-dependent endometrial cancer cell proliferation. The inhibitory effect of the antisense oligodeoxyribonucleotides on ER alpha production and ligand binding was enhanced in the presence of exogenous 17 beta-estradiol. CONCLUSION: The data suggest that antisense oligodeoxyribonucleotides against the human ER alpha have the potential of acting as anti-proliferative agents for estrogen-dependent endometrial cancers and may help in elucidating the relative roles of the two estrogen receptors, ER alpha and ER beta, in cell processes other than proliferation.
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