ArticleVirchows Archiv : an international journal of pathology2022
BCL3 expression is strongly associated with the occurrence of breast cancer relapse under tamoxifen treatment in a retrospective cohort study.
Article in Virchows Archiv : an international journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Interplay of Interleukin-1Oncology research · 2026Article
- G-quadruplex-dependent transcriptional regulation by molecular condensation in the Bcl3 promoter.Nucleic acids research · 2025Article
- Cancer-associated fibroblast driven paracrine IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma.Breast cancer research : BCR · 2025Article
- Current progress of anti‑PD‑1/PDL1 immunotherapy for glioblastoma (Review).Molecular medicine reports · 2024Review
- CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms.Nature cancer · 2024Article
- Enhancing cell death in B-cell malignancies through targeted inhibition of Bcl-3.Cell death & disease · 2024Article
- Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells.BMC cancer · 2024Article
- Suppression of Bcl3 Disrupts Viability of Breast Cancer Cells through Both p53-Dependent and p53-Independent Mechanisms via Loss of NF-κB Signalling.Biomedicines · 2024Article
- Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age.Molecular cancer · 2024Review
- ERβ1 Sensitizes and ERβ2 Desensitizes ERα-Positive Breast Cancer Cells to the Inhibitory Effects of Tamoxifen, Fulvestrant and Their Combination with All-Trans Retinoic Acid.International journal of molecular sciences · 2023Article
- A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells.Cancers · 2022Article
- Relationship of micro-RNA, mRNA and eIF Expression in Tamoxifen-Adapted MCF-7 Breast Cancer Cells: Impact of miR-1972 on Gene Expression, Proliferation and Migration.Biomolecules · 2022Article
- Biological effects and regulation of IGFBP5 in breast cancer.Frontiers in endocrinology · 2022Review
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9 authors at 4 institutions in 2 countries.
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Abstract
Patients with estrogen receptor positive breast cancer are usually receiving an anti-estrogen therapy by either aromatase inhibitors or selective estrogen receptor mediators such as tamoxifen. Nevertheless, acquired resistance to tamoxifen under treatment frequently hampers therapy. One proposed explanation for this phenomenon is the interaction of the tumor cells with cells of the tumor microenvironment via the Insulin-like growth factor RNA binding protein 5/B-cell lymphoma 3 (IGFBP5/BCL3) axis. Here we investigated whether a high expression of BCL3 either cytoplasmic or nuclear is associated with the occurrence of a relapse under anti-estrogen therapy in patients. Formaldehyde-fixed, paraffin-embedded samples of 180 breast cancer patients were analyzed for BCL3 expression by immunohistochemistry. An immunoreactive score (IRS) was calculated from staining intensity in cytoplasm and nucleus as well as the percentage of positive tumor cells. These scores were correlated with clinico-pathological parameters using cross-tabulation analysis and patients' relapse free and overall survival by Kaplan-Meier analysis and Cox regression. A tamoxifen-adapted MCF-7 derived cell line was investigated for BCL3 localization by immunofluorescence. The cytosolic BCL3-IRS significantly correlated with the proliferation marker Ki-67, and with the occurrence of a relapse under tamoxifen treatment. Nuclear score correlated only with tamoxifen-relapse. In survival analysis, both scores were highly significant prognostic factors for relapse free, but not for overall survival. This was especially obvious for estrogen receptor positive and HER2/NEU negative cases as well as lobular breast cancer. Tamoxifen-treated, but not aromatase-treated patients had a poor survival when BCL3 scores were high. A tamoxifen adapted cell line exhibited a reduced expression and mainly nuclear localization of BCL3, compared to the parental estrogen receptor positive cell-line MCF-7. Altogether, these data strongly support a function of BCL3 in tamoxifen resistance and its potential use as a predictive biomarker for tamoxifen resistance.
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