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Abstract
Introduction. Papillary thyroid cancer (PTC) is the most common tumor among endocrine tumors. The key molecular mechanisms of PTC progression are the activation of the b-RAF oncogene and the MAPK signaling pathway with the formation of an aggressive invasive and metastatic potential. Steroid receptor coactivators SRC-1 and SRC-3 are molecular factors with broad specificity capable of regulating the transcriptional activity of nuclear factors associated with oncogenesis.
Aim. To study the expression and content of SRC-1 and SRC-3 in the papillary thyroid cancer tissue of patients with PTC, depending on transcription and growth factors, steroid hormone receptors and clinicomorphological parameters.
Materials and Methods. The study included 82 patients treated at the clinics of the Research Institute of Oncology at the Tomsk National Research Medical Center: 46 patients with PTC T1-4N0-1M0 and 36 patients with benign thyroid pathologies. Molecular marker expressions were assessed using real-time PCR. Protein content was evaluated by Western blotting. The BRAFV600E mutation was determined using allele-specific PCR.
Results. Associations were found between the expression and content of co-activators of steroid receptors and the PTC subtype, the presence of the BRAFV600E mutation, tumor size, and signs of tumor invasion into the thyroid capsule. The molecular profile of the tumor with the BRAFV600E mutation was associated with divergent changes in the expression and content of SRC-1 and SRC-3. Significant elevation of SRC-3 protein content was observed in BRAFV600E mutated samples resulting in increased expression of NF-ĸB, HIF-1, VHL, and VEGF.
Conclusion. High levels of SRC-3 expression and content are associated with the development of aggressive tumor behavior. The presence of the BRAFV600E mutation is associated with the activation of transcription factors NF-ĸB, HIF-1, Brn-3α, VEGF, which are also detected in tumor invasion into the thyroid capsule.
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