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Abstract
Overexpression of the c‑Myc transcription factor is common in human breast cancer, yet gene amplification or increased transcription accounts for only a subset of cases. This thesis investigates increased c‑Myc protein stability as an alternative mechanism underlying c‑Myc overexpression. c‑Myc stability was found to be elevated in breast cancer cell lines and primary tumors, associated with increased phosphorylation at serine 62 and decreased phosphorylation at threonine 58. Deregulation of the tumor suppressor Axin1, including altered expression and splice variant usage, was shown to impair c‑Myc degradation and enhance its oncogenic activity. Additionally, activation of the HER2 receptor increased c‑Myc stability and transcriptional activity through pathways regulating serine 62 phosphorylation. Together, these findings identify dysregulated c‑Myc protein stability as a key mechanism in breast cancer and highlight potential targets for Myc‑directed therapies.