The role of ER-α36 and RUNX2 interaction in breast cancer progression.

Authors

Jia Sun, Xin Guan, Hongyan Li, Xiaoxia Shi, Xiaozhen Fu, Bingqiang Zhang, Mengmeng Chen, Chao Qu, Wei Zou

Published in

Steroids. Volume 235-236. Pages 109850. Sep 06, 2026. Epub Sep 06, 2026.

Abstract

The ER-α36 isoform is expressed in both ER-positive and ER-negative breast cancer cell lines. ER-α36 is implicated in promoting the proliferation, invasion, and metastasis of tumor cells. Runt-related transcription factor 2 (RUNX2) is widely recognized as a driver of bone-specific metastasis in breast cancer. The study aimed to examine the association between ER-α36 and RUNX2 in breast cancer and its relationship with cancer development. Immunohistochemical analysis of 25 cases revealed subcellular localization patterns of ER-α36 and RUNX2. ER-α36 showed nuclear positivity in 5 cases (20%), cytoplasmic/membranous positivity in 10 cases (40%), and combined nuclear/cytoplasmic positivity in 4 cases (16%). RUNX2 exhibited nuclear positivity in 5 cases (20%), cytoplasmic/membranous positivity in 9 cases (36%), and combined nuclear/cytoplasmic positivity in 6 cases (24%). Case-by-case analysis revealed that in specimens with nuclear ER-α36 positivity, RUNX2 was predominantly localized in the nucleus or nucleus/cytoplasm. Both proteins were predominantly expressed in grade 2 tumors. In vitro experiments, Knockdown of RUNX2 significantly reduced ER-α36 expression by 3.2-fold in MDA-MB-231 cells and by 8.9-fold in MCF-10A^CE cells (**p < 0.01 and ***p < 0.001, respectively), whereas ER-α36 knockdown significantly decreased RUNX2 expression by 2.3-fold in MDA-MB-231 cells (*p < 0.05). The results of co-immunoprecipitation showed that the two proteins were significantly associated in MCF-10A^CE and MDA-MB-231 cells. The luciferase reporter assay revealed that down-regulation of RUNX2 inhibited the binding of ER-α36 to estrogen response elements. These results suggest that RUNX2 interacts with ER-α36 and facilitates its transcriptional activation.

PMID:
42702102
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.

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