Aberrant Expression Pattern and Location of Cullin 1 are Associated with the Development of Papillary Carcinoma in Thyroid and Cyclin D1 Expression.

Abstract

Cullin 1 (Cul1) is a rigid scaffold protein of a major class of E3 ubiquitin ligase, also known as the Skp1/cullin1/F-box (SCF) complex, which is involved in cell-cycle progression. The aberrant expression of Cul1 is involved in the dysfunction of SCF E3 ligase. Previous studies have revealed an association between increased Cul1 expression and tumor progression and poor outcome in several different tumors. We constructed a tissue microarray containing 103 papillary carcinoma tissues of the thyroid and 66 normal thyroid tissues. Cul1 expression and Cyclin D1 expression were evaluated by immunohistochemistry staining, and the relationship between their expression and clinicopathological parameters were analyzed. Cytoplasmic expression of Cul1 was correlated with tumor occurrence (p < 0.001), N stage (p = 0.027), and Cyclin D1 expression (p < 0.001). Cyclin D1 expression showed a correlation with tumor occurrence (p < 0.001) and T stage (p = 0.009). On the other hand, nuclear expression of Cul1 showed a negative correlation with tumor occurrence (p < 0.001) and Cyclin D1 expression (p < 0.001). Cytoplasmic Cul1 expression was associated with tumor development and higher nodal metastasis status, supporting the idea that the SCF complex is involved in cell-cycle regulation and promotes cell proliferation. Nuclear expression of Cul1 showed inverse relationship between tumor aggressiveness factors. Our data suggest that the expression site of Cul1 may affect the function of the SFC complex and play a role in tumor progression.