Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness of Endometrial Cancer Cells

ABSTRACT

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.

KEYWORDS:

• AGR2
• Tamoxifen
• Endometrial cancer
• Breast cancer

Acknowledgments

We would like to thank K. Kanova and D. Knoflickova for their excellent technical assistance, and Dr. P. J. Coates for language editing.

Declaration of interest

The authors declare that they have no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This work was supported by GACR 13-00956S (Roman Hrstka and Lucia Sommerova), GACR 17-05957S (Jakub Faktor and Pavel Bouchal), IGA NT/13794-4/2012 (Borivoj Vojtesek), MH CZ-DRO (MMCI, 00209805) (Jan Podhorec, Hana Skoupilova), and MEYS-NPS I-LO1413 (Rudolf Nenutil, Joanna Obacz, and Michal Durech).