Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. siRNA Transfection
2.3. Protein Electrophoresis and Western Immunoblotting
2.4. Quantitative Reverse Transcription PCR
2.5. Cell Viability Assays
2.6. Clonogenic Assays
2.7. Protein-DNA Binding Assays
2.8. Double Immunofluorescence (IF) Labeling and Epifluorescence or Confocal Microscopy
2.9. Immunohistochemistry (IHC)
2.10. Semi-In Vivo Chick Embryo Xenograft Assay
2.11. Statistical Analysis
3. Results
3.1. JAM-A Regulates mRNA and Protein Expression of HER3
3.2. JAM-A or HER3 Gene Silencing Reduces Cell Viability and Levels of Survival Effector Proteins
3.3. JAM-A Expression Influences mRNA and Protein Expression of FOXA1
3.4. FOXA1 Regulates HER3 mRNA and Protein Expression
3.5. JAM-A Influences FOXA1 Transcription by Altering β-Catenin Expression and Localization
3.6. JAM-A Expression Correlates with Proliferation in a Semi-In Vivo Setting and with β-Catenin Expression in a Patient Tissue Microarray of Invasive Breast Cancer Specimens
4. Discussion
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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Parameter | n | High JAM-A | % | Low JAM-A | % | p-Value |
---|---|---|---|---|---|---|
Age (years) | 126 | 0.397 | ||||
≤50 | 18 | 9 | 16.1 | 9 | 12.9 | |
>50 | 108 | 47 | 83.9 | 61 | 87.1 | |
Tumor Size (mm) | 126 | 0.035 * | ||||
≤20 | 62 | 22 | 39.3 | 40 | 57.1 | |
>20 | 64 | 34 | 60.7 | 30 | 42.9 | |
NHG | 125 | 0.015 * | ||||
G1 | 16 | 2 | 3.6 | 14 | 20.0 | |
G2 | 56 | 25 | 46.4 | 31 | 44.3 | |
G3 | 53 | 28 | 50.0 | 25 | 35.7 | |
Molecular Subtype | 120 | 0.044 * | ||||
Luminal A | 95 | 37 | 69.8 | 58 | 86.6 | |
Luminal B | 6 | 3 | 5.7 | 3 | 4.5 | |
HER2+ | 5 | 2 | 3.8 | 3 | 4.5 | |
Triple Negative | 14 | 11 | 20.8 | 3 | 4.5 | |
ER Status | 126 | 0.010 * | ||||
Negative | 18 | 13 | 23.2 | 5 | 7.1 | |
Positive | 108 | 43 | 76.8 | 65 | 92.9 | |
PR Status | 126 | 0.003 * | ||||
Negative | 39 | 25 | 44.6 | 14 | 20.0 | |
Positive | 87 | 31 | 55.4 | 56 | 80.0 | |
HER2 Status | 123 | 0.233 | ||||
Negative | 115 | 49 | 90.7 | 66 | 95.7 | |
Positive | 8 | 5 | 9.3 | 3 | 4.3 |
Variable | n | High JAM-A | % | Low JAM-A | % | p-Value |
---|---|---|---|---|---|---|
β-catenin Expression | 120 | 0.003 * | ||||
Low | 9 | 16.4 | 27 | 41.5 | ||
High | 46 | 83.6 | 38 | 58.5 | ||
β-catenin Localization | 120 | 0.124 | ||||
Membrane | 4 | 7 | 1 | 1.5 | ||
Cytoplasm/Nucleus | 44 | 80 | 49 | 75.4 | ||
Absent | 7 | 13 | 15 | 23.1 | ||
Variable | n | High β-catenin | % | Low β-catenin | % | p-value |
FOXA1 Expression | 120 | 0.021 * | ||||
Low | 20 | 5.7 | 2 | 23.5 | ||
High | 65 | 94.3 | 33 | 76.5 | ||
Variable | n | High FOXA1 | % | Low FOXA1 | % | p-value |
HER3 Expression | 122 | <0.001 * | ||||
Low | 51 | 51.5 | 22 | 95.7 | ||
High | 48 | 48.5 | 1 | 4 |
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Cruz, R.G.B.; Madden, S.F.; Richards, C.E.; Vellanki, S.H.; Jahns, H.; Hudson, L.; Fay, J.; O’Farrell, N.; Sheehan, K.; Jirström, K.; et al. Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1. Cancers 2021, 13, 871. https://doi.org/10.3390/cancers13040871
Cruz RGB, Madden SF, Richards CE, Vellanki SH, Jahns H, Hudson L, Fay J, O’Farrell N, Sheehan K, Jirström K, et al. Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1. Cancers. 2021; 13(4):871. https://doi.org/10.3390/cancers13040871
Chicago/Turabian StyleCruz, Rodrigo G. B., Stephen F. Madden, Cathy E. Richards, Sri HariKrishna Vellanki, Hanne Jahns, Lance Hudson, Joanna Fay, Naoimh O’Farrell, Katherine Sheehan, Karin Jirström, and et al. 2021. "Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1" Cancers 13, no. 4: 871. https://doi.org/10.3390/cancers13040871