Differential Modulation of Galectin-3 by Tamoxifen and Progesterone Receptor Modulators: An In Vitro and In Silico Study
7 affiliations
- 1Medical School, University of Crete, Heraklion, Greece
- 2Department of Obstetrics and Gynecology, University of Crete, Heraklion, Greece
- 32nd Department of Propedeutic Surgery, “Laiko” General Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece
- 4Independent Authority of Public Revenue, Athens, Greece
- 51st Department of Pathology, General Hospital of Athens “Laiko”, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- 61st Department of Pediatrics, University of Athens Medical School, Agia Sofia Hospital, Athens, Greece
- 7Medical School, National and Kapodistrian University of Athens, Athens, Greece
Abstract
Background/Aim: Tamoxifen remains one of the most widely used endocrine treatments for hormone-receptor-positive breast cancer. However, its partial estrogen-agonist activity in the endometrium is associated with endometrial proliferation, hyperplasia, polyps, and, rarely, carcinoma. Antiprogestins and selective progesterone receptor modulators, including mifepristone and ulipristal acetate, have been proposed as alternative or adjunctive endocrine strategies, but their effects on endometrial molecular remodeling remain insufficiently characterized. This study investigates whether Galectin-3, a multifunctional lectin that is involved in epithelial integrity, angiogenesis, receptor signaling, and tumor-associated remodeling, could serve as a candidate marker of the endometrial epithelial response to endocrine modulation.
Materials and Methods: Ishikawa endometrial adenocarcinoma cells were exposed to different concentrations of tamoxifen, mifepristone, and ulipristal acetate. Galectin-3 protein expression was evaluated using Western blot analysis, and densitometric measurements were normalized to β-actin. Complementary STRING and STITCH bioinformatics analyses were performed to examine the molecular interactions linking Galectin-3 with steroid receptor and growth-factor-associated signaling pathways.
Results: Tamoxifen produced a biphasic response, characterized by modest induction of Galectin-3 expression at low concentration and marked suppression at intermediate and high concentrations. Mifepristone preserved Galectin-3 expression at low and intermediate concentrations but reduced its expression at the highest concentration. Ulipristal acetate increased Galectin-3 expression at low-to-intermediate concentrations, followed by a return toward baseline at high concentration. STRING and STITCH analyses indicated that Galectin-3 is indirectly linked to steroid receptor signaling through growth-factor-associated pathways, particularly EGFR/ERBB- and VEGF-related networks.
Conclusion: Galectin-3 expression differs according to the type and concentration of endocrine modulator used, suggesting that it may reflect distinct endometrial epithelial responses to hormonal treatment. Galectin-3 therefore warrants further investigation as a potential biomarker for assessing endometrial safety during endocrine therapy.
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BibTeX
@article{kontogeorgi2026differential,
title = {{Differential Modulation of Galectin-3 by Tamoxifen and Progesterone Receptor Modulators: An In Vitro and In Silico Study}},
author = {ADAMANTIA KONTOGEORGI and IOANNIS BOUTAS and GEORGE AGROGIANNIS and DIMITRIOS KALAITZIS and TATIANA S. DRIVA and EMMANOUIL ZOUMAKIS and SOPHIA N. KALANTARIDOU and ANTONIOS MAKRIGIANNAKIS},
journal = {In Vivo},
year = {2026},
month = oct,
doi = {10.21873/invivo.14487},
url = {https://doi.org/10.21873/invivo.14487},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Differential Modulation of Galectin-3 by Tamoxifen and Progesterone Receptor Modulators: An In Vitro and In Silico Study
AU - ADAMANTIA KONTOGEORGI
AU - IOANNIS BOUTAS
AU - GEORGE AGROGIANNIS
AU - DIMITRIOS KALAITZIS
AU - TATIANA S. DRIVA
AU - EMMANOUIL ZOUMAKIS
AU - SOPHIA N. KALANTARIDOU
AU - ANTONIOS MAKRIGIANNAKIS
PY - 2026
DA - 2026/10/29
JO - In Vivo
DO - 10.21873/invivo.14487
UR - https://doi.org/10.21873/invivo.14487
AB - Background/Aim: Tamoxifen remains one of the most widely used endocrine treatments for hormone-receptor-positive breast cancer. However, its partial estrogen-agonist activity in the endometrium is associated with endometrial proliferation, hyperplasia, polyps, and, rarely, carcinoma. Antiprogestins and selective progesterone receptor modulators, including mifepristone and ulipristal acetate, have been proposed as alternative or adjunctive endocrine strategies, but their effects on endometrial molecular remodeling remain insufficiently characterized. This study investigates whether Galectin-3, a multifunctional lectin that is involved in epithelial integrity, angiogenesis, receptor signaling, and tumor-associated remodeling, could serve as a candidate marker of the endometrial epithelial response to endocrine modulation. Materials and Methods: Ishikawa endometrial adenocarcinoma cells were exposed to different concentrations of tamoxifen, mifepristone, and ulipristal acetate. Galectin-3 protein expression was evaluated using Western blot analysis, and densitometric measurements were normalized to β-actin. Complementary STRING and STITCH bioinformatics analyses were performed to examine the molecular interactions linking Galectin-3 with steroid receptor and growth-factor-associated signaling pathways. Results: Tamoxifen produced a biphasic response, characterized by modest induction of Galectin-3 expression at low concentration and marked suppression at intermediate and high concentrations. Mifepristone preserved Galectin-3 expression at low and intermediate concentrations but reduced its expression at the highest concentration. Ulipristal acetate increased Galectin-3 expression at low-to-intermediate concentrations, followed by a return toward baseline at high concentration. STRING and STITCH analyses indicated that Galectin-3 is indirectly linked to steroid receptor signaling through growth-factor-associated pathways, particularly EGFR/ERBB- and VEGF-related networks. Conclusion: Galectin-3 expression differs according to the type and concentration of endocrine modulator used, suggesting that it may reflect distinct endometrial epithelial responses to hormonal treatment. Galectin-3 therefore warrants further investigation as a potential biomarker for assessing endometrial safety during endocrine therapy.
SN - 0258-851X
SN - 1791-7549
ER -