Estrogen receptor β as a potential target for lymphoma therapy

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Konstantin Yakimchuk

Accepted Abstracts: J Cancer Sci Ther

Abstract :

Cellular signaling by estrogens is mediated by estrogen receptors α (ERα) and β (ERβ). Estrogens stimulate proliferation via ERα, but inhibit proliferation and promote differentiation via ERβ. With regard to the immune system, ERβ was found to be the dominant expressed ER. Estrogens regulate various physiological pathological processes, including cancers. Several epidemiological studies demonstrate that men have a higher incidence of B-cell lymphomas and leukemias in comparison to women, suggesting that lymphomas may be under estrogen influence. Our studies have demonstrated ERβ expression in human B cell lymphoma cell lines derived from patients with Burkitt?s (BL) and mantle cell (MCL) lymphomas. Grafting human BL and MCL lymphoma cells to immune-compromised NOD.SCID mice showed an inhibition of tumor growth following treatment with the ERβ selective agonist diarylpropionitrile (DPN). To test whether ERβ activation will inhibit lymphoma dissemination in vivo, we engrafted NOD/SCID mice subcutaneously with Raji BL cells previously shown to be able to disseminate. The numberand the sizeof tumor foci of Raji cell dissemination in liver were significantly reduced by DPN treatment of mice with Raji lymphomas. In addition, expression of a chemokine receptor CXCR4, involved in lymphoma dissemination and homing to secondary of lymphoid tissues, was found to be downregulated by DPN. These results show that ERβ agonist treatment significantly inhibits lymphoma dissemination in vivo and suggest that specifically targeting ERβ in lymphomas with ERβ agonists will therefore be useful in the treatment of B-cell lymphomas.

Biography :

Konstantin Yakimchuk has completed his MD in 1998 and PhD in immunology and genetics in 2001. He obtained his postdoctoral training at Brigham and Women?s Hospital and Harvard Medical School, Boston, USA. Currently, he is the Senior Reseacher at KarolinskaInstitutet, Stockholm, Sweden. His research is focused on the functions of estrogen receptors in immune system and hematological malignancies. His studies on estrogen receptors in lymphomas were published in Leukemia and Blood journals.