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Analysis of TLR2 in Primary Endocrine Resistant of Breast Cancer
- Source :
- Frontiers in Bioscience-Landmark, Vol 29, Iss 2, p 81 (2024)
- Publication Year :
- 2024
- Publisher :
- IMR Press, 2024.
-
Abstract
- Background: Previous clinical studies have suggested that Toll-like receptor (TLR)2 had predictive function for endocrine resistance in HER2-positive breast cancer (BCa). Nevertheless, it remains unclear whether TLR2 would relate to development of endocrine therapy resistance in triple-positive breast cancer (TPBC). Methods: Bioinformatic analysis of TLR2 was carried out through a database. Ten tumor tissues were obtained from TPBC patients who underwent surgery, with five patients displaying primary resistance to tamoxifen (TAM) with the remaining 5 being sensitive. Different levels of proteins were identified through mass spectrometry analysis and confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot. TAM-resistant cell lines (BT474-TAM) were established by continuous exposure to TAM, and TAM resistance was assessed via IC50. Additionally, TLR2 mRNA was analyzed through western blot and RT-PCR in BT474, BT474-TAM, MCF-7, and MCF10A cells. Furthermore, TLR2-specific interference sequences were utilized to downregulate TLR2 expression in BT474-TAM cells to elucidate its role in TAM resistance. Results: TLR2 had a correlation with decreased relapse-free survival in BCa patients from the GSE1456-GPL96 cohort, and it was involved in cancer development predominantly mediated by MAPK and PI3K pathways. TLR2 protein expression ranked in the top 5 proteins within the TAM-resistant group, and was 1.9 times greater than that in the sensitive group. Additionally, TLR2 mRNA and protein expression increased significantly in the established TAM-resistant BT474/TAM cell lines. The sensitivity of TAM was restored upon TLR2 downregulation in BT474/TAM cells. Conclusions: TLR2 might have a therapeutic value as it was involved in the TAM resistance in TPBC, with potential to be a marker for primary endocrine resistance.
Details
- Language :
- English
- ISSN :
- 27686701
- Volume :
- 29
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Bioscience-Landmark
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.543a72744412453f8317c35954d280e0
- Document Type :
- article
- Full Text :
- https://doi.org/10.31083/j.fbl2902081