Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction in IGF binding proteins

Endocrinology
D KleinmanY Sharoni

Abstract

A significant increase in endometrial cancer incidence in tamoxifen-treated breast cancer patients has been reported in many recent studies. The major growth stimulators of endometrial tumors are estrogens, but paradoxically, tamoxifen, a known antiestrogen, also stimulates their growth. The mode of action of estrogen can be partially explained by the modulation of insulin-like growth factor (IGF) autocrine or paracrine action. The purpose of the present study was to examine the involvement of the IGF system in the tamoxifen-stimulated growth of Ishikawa endometrial cancer cells by quantitating the IGF-I receptors and their phosphorylation, as well as membrane associated and secreted IGF-binding proteins (IGFBPs). Tamoxifen did not affect the number or affinity of IGF-I receptors. On the other hand, tamoxifen, similar to estradiol, increased IGF-I-stimulated tyrosine phosphorylation of cellular substrates. In contrast, in MCF-7 mammary cancer cells, tamoxifen reduced IGF-induced tyrosine phosphorylation in the presence of estradiol. The pure antiestrogen LY156758 did not affect Ishikawa basal cell growth but inhibited estradiol- and tamoxifen-induced growth. Growth inhibition by LY156758 of tamoxifen and estradiol-stimulated ce...Continue Reading

Citations

Jun 24, 2011·Diabetology & Metabolic Syndrome·Claire L DonohoeJohn V Reynolds
Sep 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Angela DeMicheleBrian L Strom
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Sep 29, 2001·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·A. H. N. UgwumaduP. Neven
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Mar 27, 1998·Breast Cancer Research and Treatment·E SurmaczL Sciacca
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