Galectin-3 as a Candidate Marker of Endocrine-modulator-associated Endometrial Remodeling During Breast Cancer Endocrine Therapy

Adamantia Kontogeorgi, Ioannis Boutas, Dimitrios Kalaitzis, Tatiana S. Driva, George Agrogiannis, Emmanouil Zoumakis, Sophia Kalantaridou, Antonios Makrigiannakis
In: In Vivo · 2026 · vol. 40(6) , pp. 3519–3539 · doi:10.21873/invivo.14494 · PMID:42957240 · W7224606962
Lab / animal OA: diamond CC0
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This rat and cell study found that tamoxifen induced complex endometrial hyperplasia with reduced galectin-3 expression, whereas mifepristone and ulipristal acetate caused simple hyperplasia or retained normal morphology, supporting galectin-3 as a marker of endocrine-modulator-associated endometrial remodeling.

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Abstract

Background/Aim: Breast cancer endocrine therapies may induce endometrial alterations, but the endometrial effects of antiprogestins remain incompletely defined. This study evaluated the effects of tamoxifen, mifepristone, and ulipristal acetate on endometrial morphology and galectin-3 expression, with the aim of exploring galectin-3 as a candidate marker of endocrine-modulator-associated endometrial remodeling. Materials and Methods: Endometrial effects were examined in a rat mammary carcinogenesis model treated with tamoxifen, mifepristone, ulipristal acetate, or vehicle control. Uterine tissues were assessed by histology and galectin-3 immunohistochemistry. Complementary in vitro experiments in Ishikawa endometrial adenocarcinoma cells evaluated agent- and dose-associated galectin-3 protein-expression patterns by western blotting. Histological outcomes and in vitro fold-change values were summarized descriptively. Results: In the analyzed cohort, tamoxifen-treated animals showed the highest descriptive proportion of complex endometrial hyperplasia, whereas mifepristone and ulipristal acetate were associated predominantly with simple hyperplastic changes. Normal endometrial morphology was retained in selected mifepristone- and ulipristal acetate-treated animals and in all control animals. Galectin-3 immunoreactivity was low but detectable in morphologically normal endometrium, whereas hyperplastic lesions showed no detectable galectin-3 immunoreactivity under the staining conditions used. In Ishikawa cells, galectin-3 expression showed agent-specific fold-change patterns: tamoxifen and mifepristone were associated with reduced expression at higher concentrations, while ulipristal acetate showed a non-monotonic pattern with increased expression at low and intermediate concentrations and return toward baseline at the highest concentration. Conclusion: In this exploratory model, endocrine-modulator-associated hyperplastic endometrial remodeling was accompanied by reduced or undetectable galectin-3 immunoreactivity, while low-level expression was retained in morphologically normal endometrium. These findings support further investigation of galectin-3 as a candidate marker of endocrine-associated endometrial remodeling, but validation in larger animal cohorts and human endometrial samples from treated patients is required.

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SciLite annotations

chemicals 15
tamoxifen mifepristone ulipristal acetate tamoxifen mifepristone ulipristal acetate tamoxifen mifepristone ulipristal acetate mifepristone ulipristal tamoxifen ulipristal acetate
organisms 5
zitter rats multicellular animals multicellular animals rodents human

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