This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Huynh, H. T. Articles by Pollak, M. Search for Related Content PubMed PubMed Citation Articles by Huynh, H. T. Articles by Pollak, M.

In Vivo Inhibition of Insulin-like Growth Factor I Gene Expression by Tamoxifen¹

Departments of Medicine and Oncology, McGill University [M. P.], and the Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital [M. P., H. T. H., E. T., L. W.], Montréal. Québec, Canada

Tamoxifen, a partial antagonist to the estrogen receptor, is widely used in the treatment of breast cancer and is currently being evaluated as a breast cancer preventative agent in large-scale clinical trials. Recent clinical research has demonstrated that tamoxifen administration is associated with a reduction of serum insulin-like growth factor I (IGF-I) concentration. We demonstrate here that tamoxifen, when administered in an in vivo experimental system previously used to demonstrate its cytostatic effect on breast cancer cell proliferation, inhibits the expression of the IGF-I gene in common target organs for breast cancer metastasis. Furthermore, while our prior experimental studies have demonstrated an inhibitory effect of tamoxifen on growth hormone output, we show here for the first time that the suppression of IGF-I gene expression associated with tamoxifen administration is in part a consequence of a pituitary-independent action of the drug. Because IGF-I is a potent mitogen for breast cancer cells, this newly described activity of tamoxifen may contribute to its antineoplastic properties, particularly with regard to inhibition of metastasis seen both in animal models and clinically.

¹ Supported by grants to M. P. by the National Cancer Institute of Canada and the Canadian Breast Cancer Foundation.

² To whom requests for reprints should be addressed, at Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montréal, Québec, Canada H3T 1E2.

Received 12/23/92. Accepted 3/ 5/93.

This article has been cited by other articles:

				H. Hung Suppression of ps20 Expression in the Rat Uterus by Tamoxifen and Estrogens Endocrinology, May 1, 2005; 146(5): 2388 - 2396. [Abstract] [Full Text] [PDF]

				R. A. Lubet, K. Christov, N. P. Nunez, S. D. Hursting, V. E. Steele, M.M. Juliana, I. Eto, and C. J. Grubbs Efficacy of Targretin on methylnitrosourea-induced mammary cancers: prevention and therapy dose-response curves and effects on proliferation and apoptosis Carcinogenesis, February 1, 2005; 26(2): 441 - 448. [Abstract] [Full Text] [PDF]

				C. K. Ong, C. Y. Ng, C. Leong, C. P. Ng, C. S. Ong, T. T. T. Nguyen, and H. Huynh Structural Characterization of Three Novel Rat OKL38 Transcripts, Their Tissue Distributions, and Their Regulation by Human Chorionic Gonadotropin Endocrinology, October 1, 2004; 145(10): 4763 - 4774. [Abstract] [Full Text] [PDF]

				J. M. Fitts, R. M. Klein, and C. A. Powers Comparison of Tamoxifen and Testosterone Propionate in Male Rats: Differential Prevention of Orchidectomy Effects on Sex Organs, Bone Mass, Growth, and the Growth Hormone-IGF-I Axis J Androl, July 1, 2004; 25(4): 523 - 534. [Abstract] [Full Text] [PDF]

				H. Yu, X.-O. Shu, B. D. L. Li, Q. Dai, Y.-T. Gao, F. Jin, and W. Zheng Joint Effect of Insulin-like Growth Factors and Sex Steroids on Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1067 - 1073. [Abstract] [Full Text] [PDF]

				T.-T. Phan, I. J. Lim, B. H. Bay, R. Qi, M. T. Longaker, S.-T. Lee, and H. Huynh Role of IGF system of mitogens in the induction of fibroblast proliferation by keloid-derived keratinocytes in vitro Am J Physiol Cell Physiol, April 1, 2003; 284(4): C860 - C869. [Abstract] [Full Text] [PDF]

				I. J. Lim, T.-T. Phan, B.-H. Bay, R. Qi, H. Huynh, W. T.-L. Tan, S.-T. Lee, and M. T. Longaker Fibroblasts cocultured with keloid keratinocytes: normal fibroblasts secrete collagen in a keloidlike manner Am J Physiol Cell Physiol, July 1, 2002; 283(1): C212 - C222. [Abstract] [Full Text] [PDF]

				J. M. Fitts, R. M. Klein, and C. A. Powers Estrogen and Tamoxifen Interplay with T3 in Male Rats: Pharmacologically Distinct Classes of Estrogen Responses Affecting Growth, Bone, and Lipid Metabolism, and Their Relation to Serum GH and IGF-I Endocrinology, October 1, 2001; 142(10): 4223 - 4235. [Abstract] [Full Text] [PDF]

				H. Huynh, C. Y. Ng, C. K. Ong, K. B. Lim, and T. W. M. Chan Cloning and Characterization of a Novel Pregnancy-Induced Growth Inhibitor in Mammary Gland Endocrinology, August 1, 2001; 142(8): 3607 - 3615. [Abstract] [Full Text] [PDF]

				T. W. Chan, M. Pollak, and H. Huynh Inhibition of Insulin-like Growth Factor Signaling Pathways in Mammary Gland by Pure Antiestrogen ICI 182,780 Clin. Cancer Res., August 1, 2001; 7(8): 2545 - 2554. [Abstract] [Full Text] [PDF]

				H. Huynh, C. Y. Ng, K. B. Lim, C. K. Ong, C. S. Ong, E. Tran, T. T. Tuyen Nguyen, and T. W. M. G. Chan Induction of UO-44 Gene Expression by Tamoxifen in the Rat Uterus and Ovary Endocrinology, July 1, 2001; 142(7): 2985 - 2995. [Abstract] [Full Text] [PDF]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				R. E. Favoni and A. De Cupis The Role of Polypeptide Growth Factors in Human Carcinomas: New Targets for a Novel Pharmacological Approach Pharmacol. Rev., June 1, 2000; 52(2): 179 - 206. [Abstract] [Full Text] [PDF]

				A. Jilani, D. Ramotar, C. Slack, C. Ong, X. M. Yang, S. W. Scherer, and D. D. Lasko Molecular Cloning of the Human Gene, PNKP, Encoding a Polynucleotide Kinase 3'-Phosphatase and Evidence for Its Role in Repair of DNA Strand Breaks Caused by Oxidative Damage J. Biol. Chem., August 20, 1999; 274(34): 24176 - 24186. [Abstract] [Full Text] [PDF]

				I. Suzuma, M. Mandai, H. Takagi, K. Suzuma, A. Otani, H. Oh, K. Kobayashi, and Y. Honda 17 {beta}-Estradiol Increases VEGF Receptor-2 and Promotes DNA Synthesis in Retinal Microvascular Endothelial Cells Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 2122 - 2129. [Abstract] [Full Text] [PDF]

				J. M. Fitts, R. M. Klein, and C. A. Powers Comparison of Tamoxifen Effects on the Actions of Triiodothyronine or Growth Hormone in the Ovariectomized-Hypothyroid Rat J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 392 - 402. [Abstract] [Full Text]

				T. M. Abdelbaky, G. B. Brock, and H. Huynh Improvement of Erectile Function in Diabetic Rats by Insulin: Possible Role of the Insulin-Like Growth Factor System Endocrinology, July 1, 1998; 139(7): 3143 - 3147. [Abstract] [Full Text] [PDF]

				H. Huynh, X. Yang, and M. Pollak Estradiol and Antiestrogens Regulate a Growth Inhibitory Insulin-like Growth Factor Binding Protein 3 Autocrine Loop in Human Breast Cancer Cells J. Biol. Chem., January 12, 1996; 271(2): 1016 - 1021. [Abstract] [Full Text] [PDF]