BACKGROUND: Menin is a tumor suppressor encoded by Men1 that is mutated in the human-inherited tumor syndrome--multiple endocrine neoplasia type 1. Menin binds to estrogen receptors (ER) to enhance estrogen activity in breast cancer cells. AIM: Our clinical study showed that the outcome in the case of menin-positive tumors was worse than in the case of menin-negative tumors. We examined the role of raloxifene on the cell growth in a menin-positive breast cancer cell line. MATERIAL AND METHODS: To examine the mechanism of raloxifene on menin-dependent activation of ER, we employed the mammalian two-hybrid system. We have established a breast cancer cell line that stably expresses menin. Using these cells, we have examined the effect of raloxifene and tamoxifen on cell growth of menin-transfected cells. RESULTS: The expression of activation function (AF)-2 enhanced menin-mediated luciferase expression in the mammalian two-hybrid assay. Raloxifene attenuated the effect of menin on estrogen response element-luciferase activation, indicating that raloxifene inhibited the binding of menin to AF-2. Raloxifene significantly inhibited the growth of menin-transfected cells in a dose-dependent manner. Tamoxifen also inhibited menin-transfected MCF-7 cells; however, this inhibition was much less than that of raloxifene. CONCLUSION: Raloxifene inhibits the binding of menin to the AF-2 domain of ERα, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer.
BACKGROUND:Menin is a tumor suppressor encoded by Men1 that is mutated in the human-inherited tumor syndrome--multiple endocrine neoplasia type 1. Menin binds to estrogen receptors (ER) to enhance estrogen activity in breast cancer cells. AIM: Our clinical study showed that the outcome in the case of menin-positive tumors was worse than in the case of menin-negative tumors. We examined the role of raloxifene on the cell growth in a menin-positive breast cancer cell line. MATERIAL AND METHODS: To examine the mechanism of raloxifene on menin-dependent activation of ER, we employed the mammalian two-hybrid system. We have established a breast cancer cell line that stably expresses menin. Using these cells, we have examined the effect of raloxifene and tamoxifen on cell growth of menin-transfected cells. RESULTS: The expression of activation function (AF)-2 enhanced menin-mediated luciferase expression in the mammalian two-hybrid assay. Raloxifene attenuated the effect of menin on estrogen response element-luciferase activation, indicating that raloxifene inhibited the binding of menin to AF-2. Raloxifene significantly inhibited the growth of menin-transfected cells in a dose-dependent manner. Tamoxifen also inhibited menin-transfected MCF-7 cells; however, this inhibition was much less than that of raloxifene. CONCLUSION:Raloxifene inhibits the binding of menin to the AF-2 domain of ERα, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer.
Authors: S C Chandrasekharappa; S C Guru; P Manickam; S E Olufemi; F S Collins; M R Emmert-Buck; L V Debelenko; Z Zhuang; I A Lubensky; L A Liotta; J S Crabtree; Y Wang; B A Roe; J Weisemann; M S Boguski; S K Agarwal; M B Kester; Y S Kim; C Heppner; Q Dong; A M Spiegel; A L Burns; S J Marx Journal: Science Date: 1997-04-18 Impact factor: 47.728
Authors: Koen M A Dreijerink; Klaas W Mulder; G Sebastiaan Winkler; Jo W M Höppener; Cornelis J M Lips; H Th Marc Timmers Journal: Cancer Res Date: 2006-05-01 Impact factor: 12.701
Authors: Koen M A Dreijerink; Radhika A Varier; Rick van Nuland; Roel Broekhuizen; Gerlof D Valk; Jacqueline E van der Wal; Cornelis J M Lips; J Alain Kummer; H Th Marc Timmers Journal: Mol Cell Endocrinol Date: 2009-09-01 Impact factor: 4.102