This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thompson, E. W. Articles by Lippman, M. E. Search for Related Content PubMed PubMed Citation Articles by Thompson, E. W. Articles by Lippman, M. E.

Differential Regulation of Growth and Invasiveness of MCF-7 Breast Cancer Cells by Antiestrogens¹

Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research [E. W. T., R. R., T. B. S., A. A., J. G., G. R. M.], and Medical Breast Cancer Section, Medicine Branch, National Cancer Institute [R. B. D., M. E. L.], NIH, Bethesda, Maryland 20892

Estrogen increases the ability of the estrogen-dependent MCF-7 human breast cancer cell line to both proliferate and invade through an artificial basement membrane. In studying the response of MCF-7 cells to various antiestrogens, we found that 4-hydroxytamoxifen and tamoxifen inhibited cell proliferation but increased their invasiveness. In contrast, the structurally unrelated benzothiophene antiestrogens, LY117018 and LY156758, were potent antiproliferative agents which did not stimulate invasiveness. The differential effects of these antiestrogenic agents on invasion correlated with changes in production of collagenase IV, while no significant change was seen in the chemotactic activity of the cells. Invasiveness was increased by 17ß-estradiol or 4-hydroxytamoxifen after a few hours of treatment and was rapidly lost when 17ß-estradiol was withdrawn. Stimulation of invasiveness with 17ß-estradiol was blocked by the antiestrogen, LY117018. Cells from the MDA-MB-231 line which lacks estrogen receptors were not affected by estrogen or antiestrogen in terms of proliferation or invasion. These studies indicate that the invasiveness of MCF-7 cells is regulated by antiestrogens through the estrogen receptor and may be mediated by collagenase IV activity. Antiestrogens which reduce both the proliferation and invasiveness of these cells may be interesting new candidates for clinical application.

¹ This work, T. B. S., and E. W. T. were supported by the Breast Cancer Study Group, Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, NIH.

Received 7/ 5/88. Revised 8/31/88. Accepted 9/ 6/88.

This article has been cited by other articles:

				C. Qiu, L. Shan, M. Yu, and E. G. Snyderwine Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Carcinogenesis, April 1, 2005; 26(4): 763 - 769. [Abstract] [Full Text] [PDF]

				J. M. Pellikainen, K. M. Ropponen, V. V. Kataja, J. K. Kellokoski, M. J. Eskelinen, and V.-M. Kosma Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Breast Cancer with a Special Reference to Activator Protein-2, HER2, and Prognosis Clin. Cancer Res., November 15, 2004; 10(22): 7621 - 7628. [Abstract] [Full Text] [PDF]

				H. Liu, E.-S. Lee, C. Gajdos, S. T. Pearce, B. Chen, C. Osipo, J. Loweth, K. McKian, A. De Los Reyes, L. Wing, et al. Apoptotic Action of 17{beta}-Estradiol in Raloxifene-Resistant MCF-7 Cells In Vitro and In Vivo J Natl Cancer Inst, November 5, 2003; 95(21): 1586 - 1597. [Abstract] [Full Text] [PDF]

				J.-W. Park, M. W. Yeh, M. G. Wong, M. Lobo, W. C. Hyun, Q.-Y. Duh, and O. H. Clark The Heat Shock Protein 90-Binding Geldanamycin Inhibits Cancer Cell Proliferation, Down-Regulates Oncoproteins, and Inhibits Epidermal Growth Factor-Induced Invasion in Thyroid Cancer Cell Lines J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3346 - 3353. [Abstract] [Full Text] [PDF]

				N. Platet, S. Cunat, D. Chalbos, H. Rochefort, and M. Garcia Unliganded and Liganded Estrogen Receptors Protect against Cancer Invasion via Different Mechanisms Mol. Endocrinol., July 1, 2000; 14(7): 999 - 1009. [Abstract] [Full Text]

				W. Khovidhunkit and D. M. Shoback Clinical Effects of Raloxifene Hydrochloride in Women Ann Intern Med, March 2, 1999; 130(5): 431 - 439. [Abstract] [Full Text] [PDF]

				K. Yao and V. C. Jordan Questions about Tamoxifen and the Future Use of Antiestrogens Oncologist, April 1, 1998; 3(2): 104 - 110. [Abstract] [Full Text]

				I. Erenburg, B. Schachter, R. M. y Lopez, and L. Ossowski Loss of an Estrogen Receptor Isoform (ER{alpha}{Delta}3) in Breast Cancer and the Consequences of Its Reexpression: Interference with Estrogen-Stimulated Properties of Malignant Transformation Mol. Endocrinol., December 1, 1997; 11(13): 2004 - 2015. [Abstract] [Full Text] [PDF]

				H. A. Kester, B.-j. M. van der Leede, P. T. van der Saag, and B. van der Burg Novel Progesterone Target Genes Identified by an Improved Differential Display Technique Suggest That Progestin-induced Growth Inhibition of Breast Cancer Cells Coincides with Enhancement of Differentiation J. Biol. Chem., June 27, 1997; 272(26): 16637 - 16643. [Abstract] [Full Text] [PDF]

				S. Kim-Schulze, K. A. McGowan, S. C. Hubchak, M. C. Cid, M. B. Martin, H. K. Kleinman, G. L. Greene, and H. W. Schnaper Expression of an Estrogen Receptor by Human Coronary Artery and Umbilical Vein Endothelial Cells Circulation, September 15, 1996; 94(6): 1402 - 1407. [Abstract] [Full Text]

				D. E. Morales, K. A. McGowan, D. S. Grant, S. Maheshwari, D. Bhartiya, M. C. Cid, H. K. Kleinman, and H. W. Schnaper Estrogen Promotes Angiogenic Activity in Human Umbilical Vein Endothelial Cells In Vitro and in a Murine Model Circulation, February 1, 1995; 91(3): 755 - 763. [Abstract] [Full Text]