T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson, Advances in biology of multiple myeloma: clinical applications, Blood, vol.104, pp.607-618, 2004.

K. Bommert, R. C. Bargou, and T. Stühmer, Signalling and survival pathways in multiple myeloma, Eur J Cancer, vol.42, pp.1574-1580, 2006.

S. L. Mooberry, New insights into 2-methoxyestradiol, a promising antiangiogenic and antitumor agent, Curr Opin Oncol, vol.15, pp.425-430, 2003.

D. Chauhan, L. Catley, T. Hideshima, G. Li, R. Leblanc et al., -methoxyestradiol overcomes drug resistance in multiple myeloma, Blood, vol.100, issue.2, pp.2187-2194, 2002.

D. Dingli, M. Timm, S. J. Russell, T. E. Witzig, and S. V. Rajkumar, Promising preclinical activity of 2-methoxyestradiol in multiple myeloma, Clin Cancer Res, vol.8, pp.3948-3954, 2002.

D. Chauhan, G. Li, D. Auclair, T. Hideshima, P. Richardson et al., Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma cells using oligonucleotide arrays, Blood, vol.101, pp.3606-3614, 2003.

L. H. Wang, X. Y. Yang, K. Mihalic, X. W. Li, D. Farrar et al., Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3, J Biol Chem, vol.276, pp.31839-31844, 2001.

A. C. Bharti, S. Shishodia, J. M. Reuben, D. Weber, R. Alexanian et al., Nuclear factor-kappa B and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis, Blood, vol.103, pp.3175-3184, 2004.

M. Chatterjee, T. Stühmer, P. Herrmann, K. Bommert, B. Dörken et al., Combined disruption of both the MEK/ERK and the IL-6R/STAT3 pathways is required to induce apoptosis of multiple myeloma cells in the presence of bone marrow stromal cells, Blood, vol.104, pp.3712-3721, 2004.

T. Otsuki, O. Yamada, J. Kurebayashi, T. Moriya, H. Sakaguchi et al., Estrogen receptors in human myeloma cells, Cancer Res, vol.60, pp.1434-1441, 2000.

J. Gauduchon, F. Gouilleux, S. Maillard, V. Marsaud, J. Renoir et al., 4-hydroxytamoxifen inhibits proliferation of multiple myeloma cells in vitro through down-regulation of c-Myc, up-regulation of p27 Kip1 , and modulation of Bcl-2 family members, Clin Cancer Res, vol.11, pp.2345-2354, 2005.

S. P. Treon, G. Teoh, M. Urashima, A. Ogata, D. Chauhan et al., Anti-estrogens induce apoptosis of multiple myeloma cells, Blood, vol.92, pp.1749-1757, 1998.

V. C. Jordan, SERMs: meeting the promise of multifunctional medicines, J Natl Cancer Inst, vol.99, pp.350-356, 2007.

S. Olivier, P. Close, E. Castermans, L. De-leval, S. Tabruyn et al., Raloxifeneinduced myeloma cell apoptosis: a study of nuclear factor-?B inhibition and gene expression signature, Mol Pharmacol, vol.69, pp.1615-1623, 2006.

A. Howell, Pure oestrogen antagonists for the treatment of advanced breast cancer, Endocr Relat Cancer, vol.13, pp.689-706, 2006.

S. Maillars, J. Gauduchon, V. Marsaud, F. Gouilleux, E. Connault et al., Improved antitumoral properties of pure antiestrogen RU 58668-loaded liposomes in multiple myeloma, J Steroid Biochem Mol Biol, vol.100, pp.67-78, 2006.

J. M. Renoir, B. Stella, T. Ameller, E. Connault, P. Opolon et al., Improved anti-tumoral capacity of mixed and pure anti-oestrogens in breast cancer cell xenografts after their administration by entrapment in colloidal nanosystems, J Steroid Biochem Mol Biol, vol.102, pp.114-127, 2006.

P. Ascenzi, A. Bocedi, and M. Marino, Structure-function relationship of estrogen receptor alpha and beta: impact on human health, Mol Aspects Med, vol.27, pp.299-402, 2006.

E. R. Levin, Integration of the extranuclear and nuclear actions of estrogen, Mol Endocrinol, vol.19, pp.1951-1959, 2005.

D. C. Márquez and R. J. Pietras, Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells, Oncogene, vol.20, pp.5420-5430, 2001.

M. Razandi, A. Pedram, I. Merchenthaler, G. L. Greene, and E. R. Levin, Plasma membrane estrogen receptors exists and function as dimers, Mol Endocrinol, vol.18, pp.2854-2865, 2004.

A. Pedram, M. Razandai, and E. R. Levin, Nature of functional estrogen receptors at the plasma membrane, Mol Endocrinol, vol.20, pp.1996-2009, 2006.

C. Heberden, R. F. Grosse, B. Henry, C. Zagar, Y. Chaumaz et al., Lieberherr M: Detection of a raft-located estrogen receptor-like protein distinct from ER alpha, Int J Biochem Cell Biol, vol.38, pp.376-391, 2006.

R. Ponzielli, S. Katz, D. Barsyte-lovejoy, and L. Z. Penn, Cancer therapeutics: targeting the dark site of Myc, Eur J Cancer, vol.41, pp.2485-2501, 2005.

J. S. Carroll, A. Swarbrick, E. A. Musgrove, and R. L. Sutherland, Mechanisms of growth arrest by c-myc antisense oligonucleotides in MCF-7 breast cancer cells: implications for the antiproliferative effects of antiestrogens, Cancer Res, vol.62, pp.3126-3131, 2002.

S. Cariou, J. C. Donovan, W. M. Flanagan, A. Milic, N. Bhattachara et al., Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells, Proc Natl Acad Sci, vol.97, pp.9042-9046, 2000.

S. Mukherjee and S. E. Conrad, c-Myc suppresses p21 WAF1/CIP1 expression during estrogen signalling and antiestrogen resistance in human breast cancer cells

, J Biol Chem, vol.208, pp.17617-17625, 2005.

J. S. Carroll, D. K. Lynch, A. Swarbrick, J. Renoir, B. Sarcevic et al., Kip1 induces quiescence and growth factor insensitivity in tamoxifen-treated breast cancer cells, Cancer Res, vol.63, pp.4322-4326, 2003.

A. Thiantanawat, B. J. Long, and A. M. Brodie, Signaling pathways of apoptosis activated by aromatase inhibitors and antiestrogens, Cancer Res, vol.63, pp.8037-8050, 2003.

S. Alas and B. Bonavida, Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis, Clin Cancer Res, vol.9, pp.316-326, 2003.

L. Quintanilla-martinez, M. Kremer, K. Specht, J. Calzada-wack, M. Nathrath et al., Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events, Am J Pathol, vol.162, pp.1449-1461, 2003.

D. Chauhan, H. Uchiyama, Y. Akbarali, M. Urashima, K. Yamamoto et al., Multiple myeloma cell adhesioninduced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B, Blood, vol.87, pp.1104-1112, 1996.

R. Catlett-falcone, T. H. Landowski, M. M. Oshiro, J. Turkson, A. Levitzki et al., Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells, Immunity, vol.10, pp.105-115, 1999.

M. Ogawa, T. Nishiura, K. Oritani, H. Yoshida, M. Yoshimura et al., Cytokines prevent dexamethasone-induced apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in a new multiple myeloma cell line, Cancer Res, vol.60, pp.4262-4269, 2000.

T. Hideshima, M. Akiyama, T. Hayashi, P. Richardson, R. Schlossman et al., Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu, Blood, vol.101, pp.703-705, 2003.

A. Fassas, A. P. Rapoport, J. Bolaños-meade, C. Shanholtz, M. Cottlerfox et al., Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation, Leuk Lymphoma, vol.42, pp.1323-1328, 2001.

P. Compound,

C. S. Mitsiades, S. P. Treon, N. Mitsiades, Y. Shima, P. Richardson et al., TRAIL/Apo2L ligand selectively induces apoptosis and overcomes resistance in