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The Impact of Decreased GSK3β and S6K1 Expression in TNBC Patients
Tijana Tomić1, Mirjana Prvanović2, Jovan Jevtić2
1Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences "Vinča", National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Abstract:
Breast cancer is the most frequent and lethal type of cancer that affects women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, having high rate of recurrence, metastasis, and mortality, with very limited options for treatment, and a tendency to develop resistance to conventional therapy. These circumstances mean that it is necessary to develop effective therapies for TNBC patients which would circumvent resistance mechanisms. The PAM and Wnt signaling pathways are among those responsible for therapy resistance in TNBC, as they also have major roles in different cellular processes such as metabolism, proliferation, metastasis, stemness, and survival. We analysed the expression of GSK3β and S6K1 as interacting components of the two pathways in order to examine the relation between them and determine whether they could be used as predictive markers in TNBC. The expression of mRNA was examined with real-time PCR and protein expression with immunohistochemistry. Our results showed that protein expression is in line with mRNA expression. We found a positive correlation between the mRNA expressions of GSK3β and S6K1, showing their coordinated transcription. We also showed that their simultaneous low expression is unfavorable for TNBC patients and could possibly be used as a predictive marker.
Insights
Low expression of GSK3β and S6K1 proteins correlates with poor outcomes in triple-negative breast cancer (TNBC). This finding suggests these proteins could serve as predictive markers for TNBC patients, guiding treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment options and a high mortality rate.
- Therapy resistance is a major challenge in TNBC, with signaling pathways like PAM and Wnt implicated in its development.
- Understanding the molecular mechanisms underlying TNBC progression and resistance is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the relationship between GSK3β and S6K1 expression in TNBC.
- To determine if GSK3β and S6K1 can serve as predictive markers for TNBC patient outcomes.
- To explore the role of these proteins in therapy resistance within TNBC.
Main Methods:
- Analysis of messenger RNA (mRNA) expression using real-time PCR.
- Assessment of protein expression through immunohistochemistry.
- Correlation analysis between GSK3β and S6K1 mRNA and protein levels.
Main Results:
- mRNA and protein expression levels of GSK3β and S6K1 were found to be consistent.
- A positive correlation was observed between the mRNA expression of GSK3β and S6K1, indicating coordinated transcriptional regulation.
- Simultaneous low expression of GSK3β and S6K1 was associated with unfavorable outcomes for TNBC patients.
Conclusions:
- GSK3β and S6K1 expression levels are linked in TNBC.
- Low co-expression of GSK3β and S6K1 may indicate a poor prognosis in TNBC patients.
- These proteins show potential as predictive biomarkers for therapeutic strategies in triple-negative breast cancer.
