PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer
Abstract
:1. Introduction
2. Results
2.1. Nuclear PAF-AH Is Highly Expressed in BRCA1 Mutant BC Tissue and Correlates Positively with Membranous β-Catenin
2.2. Only BRCA1 Negative Cell Line HCC1937 Shows Relevant Expression of PLA2G7/PAF-AH
2.3. PLA2G7 Downregulation Enhanced Viability, Proliferation, and Motility of HCC1937 Cells
2.4. The Intracellular Distribution of β-Catenin Changed from High Expression in the Membrane to High Expression in the Nucleus by PLA2G7 Knockdown
3. Discussion
4. Materials and Methods
4.1. Ethical Approval
4.2. Patient Specimens
4.3. Immunohistochemistry and Immunocytochemistry
4.4. Staining Evaluation
4.5. Statistical Analysis
4.6. Cell Lines
4.7. Real-Time PCR
4.8. siRNA Gene Knockdown
4.9. Western Blot
4.10. Cell Viability Assays
4.11. Proliferation Assay
4.12. Wound Healing Assay
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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PAF-AH Nucleus | PAF-AH Cytoplasm | |
---|---|---|
β-catenin nucleus | ||
Cc | −0.062 | 0.018 |
P | >0.05 | >0.05 |
N | 44 | 44 |
β-catenin membrane | ||
Cc | 0.766 | 0.057 |
P | <0.001 * | >0.05 |
N | 44 | 44 |
Clinicopathological Characteristics of Patients | |||
---|---|---|---|
n (121) | Percentage [%] | ||
Histology | Invasive ductal | 80 | 66.1 |
Invasive lobular | 13 | 10.7 | |
Invasive medullary | 12 | 9.9 | |
Invasively mucinous | 1 | 0.8 | |
Unknown | 15 | 11.8 | |
Grading | 1 | 4 | 3.3 |
2 | 45 | 37.1 | |
3 | 60 | 49.6 | |
Unknown | 12 | 9.9 | |
Age | ≥60 | 29 | 24.0 |
<60 | 92 | 76.0 | |
Primary tumor expansion | Tis | 5 | 4.1 |
T1a | 3 | 2.5 | |
T1b | 13 | 10.7 | |
T1c | 22 | 21.5 | |
T2 | 43 | 36.2 | |
T3 | 12 | 9.9 | |
T4a | 2 | 1.6 | |
T4b | 2 | 1.6 | |
T4c | 1 | 0.8 | |
T4d | 6 | 5.0 | |
Tx | 12 | 9.9 | |
Nodal status | N0 | 38 | 31.4 |
N1 | 34 | 28.1 | |
N2 | 9 | 7.4 | |
N3 | 7 | 5.8 | |
Nx | 33 | 27.3 | |
Distant Metastasis | M0 | 46 | 38.0 |
M1 | 28 | 23.1 | |
Mx | 47 | 53.5 | |
BRCA1 mutation status | No BRCA1 mutation | 28 | 23.1 |
BRCA1 mutation | 22 | 18.2 | |
Unknown | 71 | 58.7 |
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Liao, Y.; Badmann, S.; Kraus, F.; Topalov, N.E.; Mayr, D.; Kolben, T.; Hester, A.; Beyer, S.; Mahner, S.; Jeschke, U.; et al. PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer. Int. J. Mol. Sci. 2023, 24, 882. https://doi.org/10.3390/ijms24010882
Liao Y, Badmann S, Kraus F, Topalov NE, Mayr D, Kolben T, Hester A, Beyer S, Mahner S, Jeschke U, et al. PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer. International Journal of Molecular Sciences. 2023; 24(1):882. https://doi.org/10.3390/ijms24010882
Chicago/Turabian StyleLiao, Yue, Susann Badmann, Fabian Kraus, Nicole Elisabeth Topalov, Doris Mayr, Thomas Kolben, Anna Hester, Susanne Beyer, Sven Mahner, Udo Jeschke, and et al. 2023. "PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer" International Journal of Molecular Sciences 24, no. 1: 882. https://doi.org/10.3390/ijms24010882