Research Papers:

Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

Gergely Talaber, Konstantin Yakimchuk, Jiyu Guan, Jose Inzunza and Sam Okret _

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Oncotarget. 2016; 7:20718-20727. https://doi.org/10.18632/oncotarget.7843

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Gergely Talaber1, Konstantin Yakimchuk1, Jiyu Guan1, Jose Inzunza1, Sam Okret1

1Department of Biosciences and Nutrition, Karolinska Institutet, NOVUM, Huddinge, Sweden

Correspondence to:

Sam Okret, e-mail: [email protected]

Keywords: lymphoma, sex hormones, androgens, aromatase inhibitor, gender difference

Received: November 09, 2015     Accepted: February 20, 2016     Published: March 02, 2016


Most lymphomas show higher incidence and poorer prognosis in males compared to females. However, the endocrine contribution to this gender difference is not entirely known. Here we show that castration accelerates lymphoma growth in C57BL6 male mice grafted with murine EG7 T cell lymphoma cells. However, the androgen receptor antagonist Bicalutamide did not affect lymphoma growth, suggesting no impact of androgen receptor signaling on lymphoma progression. In contrast, inhibition of androgen-to-estrogen conversion by the aromatase inhibitor (AI) Letrozole induced faster lymphoma growth in mice, suggesting that androgens impact lymphoma growth through its conversion to estrogens. This was supported by the inability of dihydrotestosterone, which is not converted to estrogens by aromatase, to influence lymphoma growth in castrated male mice. Lymphoma growth was also stimulated in immunocompromised mice grafted with human B cell lymphoma (Granta-519) and treated with either reversible or irreversible AIs, showing that the blockage of estrogen synthesis caused enhanced growth of both murine T and human B cell lymphomas and with different AIs. Additionally, AI-treated EG7 lymphomas showed accelerated growth not only in male but also in intact female mice. Altogether, our results demonstrate that aromatase inhibition accelerates lymphoma growth but not androgens per se, highlighting a protective role of estrogens in lymphoma pathogenesis. These results also raise concern that the use of AIs in women with breast cancer might enhance lymphoma progression.

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