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RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kappa B signaling pathway.
J Clin Endocrinol Metab. 2003 Feb; 88(2):713-9.JC

Abstract

Previous studies indicated that the antiprogestin RU486 could directly inhibit the growth of normal and malignant human endometrial cells. However, the mechanism by which this occurs is poorly understood. In this study we explore further details of endometrial cell growth regulation by RU486. Gel shift assays using the endometrial cell line EM42 demonstrated that RU486, at concentrations ranging from 20-100 micro M, significantly stimulated the cellular binding activity of the nuclear transcription factor nuclear factor-kappa B (NF-kappa B) while having little effect on activating protein-1 (AP-1) binding. This effect on NF-kappa B binding was blocked in the presence of the NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC). The data also showed that the activity of RU486 on NF-kappa B binding correlated with the ability of this compound to induce apoptosis of EM42 cells. To investigate a cause and effect relationship between these two phenomena, we evaluated the effects of RU486 treatment on the expression of two apoptosis-related genes, bax and bcl-2, known to be regulated through NF-kappa B binding on their promoter. RT-PCR demonstrated that RU486 significantly induced bax mRNA levels, while suppressing mRNA of bcl-2. Alteration of these genes by RU486 was inhibited in the presence of 100 microM PDTC. Correspondingly, PDTC antagonized the ability of RU486 to inhibit the growth and induce apoptosis of EM42 cells. This study demonstrates that the inhibition of growth and apoptosis of human endometrial cells by RU486 involves stimulation of NF-kappa B binding with subsequent modulation of apoptosis regulatory genes bax and bcl-2.

Authors+Show Affiliations

Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12574204

Citation

Han, Shouwei, and Neil Sidell. "RU486-induced Growth Inhibition of Human Endometrial Cells Involves the Nuclear Factor-kappa B Signaling Pathway." The Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, 2003, pp. 713-9.
Han S, Sidell N. RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kappa B signaling pathway. J Clin Endocrinol Metab. 2003;88(2):713-9.
Han, S., & Sidell, N. (2003). RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kappa B signaling pathway. The Journal of Clinical Endocrinology and Metabolism, 88(2), 713-9.
Han S, Sidell N. RU486-induced Growth Inhibition of Human Endometrial Cells Involves the Nuclear Factor-kappa B Signaling Pathway. J Clin Endocrinol Metab. 2003;88(2):713-9. PubMed PMID: 12574204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kappa B signaling pathway. AU - Han,Shouwei, AU - Sidell,Neil, PY - 2003/2/8/pubmed PY - 2003/3/1/medline PY - 2003/2/8/entrez SP - 713 EP - 9 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 88 IS - 2 N2 - Previous studies indicated that the antiprogestin RU486 could directly inhibit the growth of normal and malignant human endometrial cells. However, the mechanism by which this occurs is poorly understood. In this study we explore further details of endometrial cell growth regulation by RU486. Gel shift assays using the endometrial cell line EM42 demonstrated that RU486, at concentrations ranging from 20-100 micro M, significantly stimulated the cellular binding activity of the nuclear transcription factor nuclear factor-kappa B (NF-kappa B) while having little effect on activating protein-1 (AP-1) binding. This effect on NF-kappa B binding was blocked in the presence of the NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC). The data also showed that the activity of RU486 on NF-kappa B binding correlated with the ability of this compound to induce apoptosis of EM42 cells. To investigate a cause and effect relationship between these two phenomena, we evaluated the effects of RU486 treatment on the expression of two apoptosis-related genes, bax and bcl-2, known to be regulated through NF-kappa B binding on their promoter. RT-PCR demonstrated that RU486 significantly induced bax mRNA levels, while suppressing mRNA of bcl-2. Alteration of these genes by RU486 was inhibited in the presence of 100 microM PDTC. Correspondingly, PDTC antagonized the ability of RU486 to inhibit the growth and induce apoptosis of EM42 cells. This study demonstrates that the inhibition of growth and apoptosis of human endometrial cells by RU486 involves stimulation of NF-kappa B binding with subsequent modulation of apoptosis regulatory genes bax and bcl-2. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/12574204/RU486_induced_growth_inhibition_of_human_endometrial_cells_involves_the_nuclear_factor_kappa_B_signaling_pathway_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2002-020876 DB - PRIME DP - Unbound Medicine ER -