ArticleBreast cancer research and treatment2020
Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer.
Article in Breast cancer research and treatment, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Efficacy and related factors of levonorgestrel-releasing intrauterine system combined with metformin in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial cancer: A retrospective cohort study.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Knock-out of CD73 delays the onset of HR-negative breast cancer by reprogramming lipid metabolism and is associated with increased tumor mutational burden.Molecular metabolism · 2024Article
- A prediction model for distant metastasis after isolated locoregional recurrence of breast cancer.Breast cancer research and treatment · 2023Article
- Molecular Mechanisms of Anti-Estrogen Therapy Resistance and Novel Targeted Therapies.Cancers · 2022Review
- c-Kit Induces Migration of Triple-Negative Breast Cancer Cells and Is a Promising Target for Tyrosine Kinase Inhibitor Treatment.International journal of molecular sciences · 2022Article
- FGF7/FGFR2-JunB signalling counteracts the effect of progesterone in luminal breast cancer.Molecular oncology · 2022Article
- Association Between GATA3 and Histopathological and Immunohistochemical Parameters in Early-Infiltrating Breast Carcinomas.European journal of breast health · 2022Article
- Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle and cytoskeleton regulation.Molecular genetics and genomics : MGG · 2022Article
- Molecular characterization of low-grade serous ovarian carcinoma identifies genomic aberrations according to hormone receptor expression.NPJ precision oncology · 2022Article
- The active kinome: The modern view of how active protein kinase networks fit in biological research.Current opinion in pharmacology · 2022Review
- Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors.Oncotarget · 2022Article
- Lost but Not Least-Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer.Cancers · 2021Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to assess protein tyrosine kinase profiles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profiles ER, PR, and HER2. EXPERIMENTAL
designPamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+ breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR.
resultsIn ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2-. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identified as responsible for the differential phosphorylation between PR- and PR+ in ER+/HER2- tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2- breast cancers. Twenty four kinase-encoding genes were identified as differentially expressed between PR+ and PR-, dividing ER+/HER2- samples in two distinct clusters with significant differences in survival (p < 0.05). Four kinase genes, LCK, FRK, FGFR4, and MST1R, were identified as potential direct targets of PR.
conclusionsOur results suggest that the PR status has a profound effect on tyrosine kinases, especially for FGFR4 and LCK genes, in ER+/HER2- breast cancer patients. The influence of these genes on the PI3K/AKT signaling pathway may potentially lead to novel drug targets for ER+/PR- breast cancer patients.
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