Abstract
A direct association has been shown between Cyclin D1 and C-myc gene expressions and the proliferation of human thyroid tumor cells. Our previous study showed that increased β catenin led to a reduction in disease-free probability in patients with papillary thyroid cancer. This study was designed to investigate Cyclin D1 and C-myc genes as targets for β catenin function in PTC and to determine the association between genes expression and staging, recurrence, metastasis, and disease-free survival of PTC. This study was conducted via a thorough investigation of available data from medical records as well as paraffin blocks of 77 out of 400 patients over a 10-year period. Cyclin D1 and C-myc gene expression levels were measured using real-time polymerase chain reaction (RT-PCR) and the Kaplan-Meier method was used to evaluate disease-free survival. Higher levels of Cyclin D1 and C-myc gene expressions were observed in patients with recurrence by 8.5 (P = 0.004) and 19.5 (p = 0.0001) folds, respectively. A significant positive correlation was found between Cyclin D1 expression and the cumulative dose of radioactive iodine received by patients (r = −0.2, p value = 0.03). The ten-year survival rate in the patients included in this study was 98.25% while disease-free survival was 48.1%. Higher Cyclin D1 and C-myc gene expression levels were observed in patients with recurrence/distant metastasis. Inversely, lower expression of Cyclin D1 and C-myc genes were associated with better survival of patients (SD, 0.142-0.052) (Mantel-Cox test, P = 0.002). The enhancement of Cyclin D1 and C-myc gene expression may be a potential mechanism for recurrence and aggressiveness of PTC.
Highlights
A direct association has been shown between Cyclin D1 and C-myc gene expressions and the proliferation of human thyroid tumor cells
Eleven percent cyclin D1 amplification, including 17% of B-RAF V600E melanoma is seen in melanoma, that suggests a potential role of cyclin D1 in intrinsic resistance to B-RAF inhibitors
We found a direct relationship between β catenin gene expression and recurrence, TNM (Tumor, Node, Metastasis) stage in PTC17
Summary
A direct association has been shown between Cyclin D1 and C-myc gene expressions and the proliferation of human thyroid tumor cells. There are several transcription factors in the Wnt-mediated signaling pathway that are involved in the expression of Wnt/β-cat target genes, such as those encoding C-Myc and Cyclin D1 In this pathway, upon accumulation www.nature.com/scientificreports of β-cat, this protein enters the cell nucleus and interacts with members of the T-cell factor and lymphoid enhancer factor 1 (LEF-1), family of transcription factors. Upon accumulation www.nature.com/scientificreports of β-cat, this protein enters the cell nucleus and interacts with members of the T-cell factor and lymphoid enhancer factor 1 (LEF-1), family of transcription factors These transcription factors stimulate the expression of Wnt/β-cat target genes, including those encoding C-Myc and Cyclin D1. Transcription of these genes when it is not necessary for cells to proliferate may result in unrestrained growth of cells and tumor development[8]
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