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Estrogen-mediated post transcriptional down-regulation of P-glycoprotein in MDR1-transduced human breast cancer cells.
Cancer Sci. 2006 Nov; 97(11):1198-204.CS

Abstract

The human multidrug resistance gene 1 (MDR1) encodes the plasma membrane P-glycoprotein (P-gp/ABCB1) that functions as an efflux pump for various anticancer agents. We recently reported that estrogens down-regulate the expression of breast cancer resistance protein (BCRP/ABCG2). In our present study we demonstrate that estrogens also down-regulate P-gp expression in the MDR1-transduced, estrogen receptor alpha (ER-alpha)-positive human breast cancer cells, MCF-7/MDR and T-47D/MDR. The P-gp expression levels in MCF-7/MDR cells treated with 100 pM estradiol were found to be 10-20-fold lower than the levels in these same cells that were cultured without estradiol. In contrast, estradiol did not affect the P-gp expression levels in the ER-alpha-negative cancer cells, MDA-MB-231/MDR and NCI/ADR-RES. Estrone and diethylstilbestrol were also found to down-regulate P-gp in MCF-7/MDR cells, but progesterone treatment did not produce this effect. Tamoxifen reversed the estradiol-mediated down-regulation of P-gp in MCF-7/MDR cells, suggesting that ER-alpha activity is necessary for the effects of estradiol upon P-gp. However, estradiol was found not to alter the MDR1 transcript levels in either MCF-7/MDR and T-47D/MDR cells, suggesting that post-transcriptional mechanisms underlie its effects upon P-gp down-regulation. MCF-7/MDR cells also showed eight-fold higher sensitivity to vincristine when treated with 100 pM estradiol, than when treated with 1 pM estradiol. These results may serve to provide a better understanding of the expression control of ABC transporters, and possibly allow for the establishment of new cancer chemotherapy strategies that would control P-gp expression in breast cancer cells and thereby increase their sensitivity to MDR1-related anticancer agents.

Authors+Show Affiliations

Department of Chemotherapy, Kyoritsu University of Pharmacy, 1-5-30 Shibakoen, Minatoku, Tokyo 105-8512, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16925584

Citation

Mutoh, Kazuyoshi, et al. "Estrogen-mediated Post Transcriptional Down-regulation of P-glycoprotein in MDR1-transduced Human Breast Cancer Cells." Cancer Science, vol. 97, no. 11, 2006, pp. 1198-204.
Mutoh K, Tsukahara S, Mitsuhashi J, et al. Estrogen-mediated post transcriptional down-regulation of P-glycoprotein in MDR1-transduced human breast cancer cells. Cancer Sci. 2006;97(11):1198-204.
Mutoh, K., Tsukahara, S., Mitsuhashi, J., Katayama, K., & Sugimoto, Y. (2006). Estrogen-mediated post transcriptional down-regulation of P-glycoprotein in MDR1-transduced human breast cancer cells. Cancer Science, 97(11), 1198-204.
Mutoh K, et al. Estrogen-mediated Post Transcriptional Down-regulation of P-glycoprotein in MDR1-transduced Human Breast Cancer Cells. Cancer Sci. 2006;97(11):1198-204. PubMed PMID: 16925584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen-mediated post transcriptional down-regulation of P-glycoprotein in MDR1-transduced human breast cancer cells. AU - Mutoh,Kazuyoshi, AU - Tsukahara,Satomi, AU - Mitsuhashi,Junko, AU - Katayama,Kazuhiro, AU - Sugimoto,Yoshikazu, Y1 - 2006/08/22/ PY - 2006/8/24/pubmed PY - 2006/11/15/medline PY - 2006/8/24/entrez SP - 1198 EP - 204 JF - Cancer science JO - Cancer Sci VL - 97 IS - 11 N2 - The human multidrug resistance gene 1 (MDR1) encodes the plasma membrane P-glycoprotein (P-gp/ABCB1) that functions as an efflux pump for various anticancer agents. We recently reported that estrogens down-regulate the expression of breast cancer resistance protein (BCRP/ABCG2). In our present study we demonstrate that estrogens also down-regulate P-gp expression in the MDR1-transduced, estrogen receptor alpha (ER-alpha)-positive human breast cancer cells, MCF-7/MDR and T-47D/MDR. The P-gp expression levels in MCF-7/MDR cells treated with 100 pM estradiol were found to be 10-20-fold lower than the levels in these same cells that were cultured without estradiol. In contrast, estradiol did not affect the P-gp expression levels in the ER-alpha-negative cancer cells, MDA-MB-231/MDR and NCI/ADR-RES. Estrone and diethylstilbestrol were also found to down-regulate P-gp in MCF-7/MDR cells, but progesterone treatment did not produce this effect. Tamoxifen reversed the estradiol-mediated down-regulation of P-gp in MCF-7/MDR cells, suggesting that ER-alpha activity is necessary for the effects of estradiol upon P-gp. However, estradiol was found not to alter the MDR1 transcript levels in either MCF-7/MDR and T-47D/MDR cells, suggesting that post-transcriptional mechanisms underlie its effects upon P-gp down-regulation. MCF-7/MDR cells also showed eight-fold higher sensitivity to vincristine when treated with 100 pM estradiol, than when treated with 1 pM estradiol. These results may serve to provide a better understanding of the expression control of ABC transporters, and possibly allow for the establishment of new cancer chemotherapy strategies that would control P-gp expression in breast cancer cells and thereby increase their sensitivity to MDR1-related anticancer agents. SN - 1347-9032 UR - https://www.unboundmedicine.com/medline/citation/16925584/Estrogen_mediated_post_transcriptional_down_regulation_of_P_glycoprotein_in_MDR1_transduced_human_breast_cancer_cells_ L2 - https://doi.org/10.1111/j.1349-7006.2006.00300.x DB - PRIME DP - Unbound Medicine ER -