Ki-67 Expression in a Cervical Cancer Organotypic Model Correlates with Growth and EGF-R Expression.

Abstract

The study objective was to measure the effects of retinoid treatment on Ki-67 expression in a cervical carcinoma organotypic culture model and to determine whether a correlation exists between retinoid effects on Ki-67 expression and effects on growth and epidermal growth factor receptor (EGF-R) expression. Organotypic cultures of the cervical carcinoma cell line were treated for 7 days with all-trans retinoic acid, 9-cis retinoic acid, or control solvent. Cultures were fixed and embedded in paraffin, and sections were stained with Ki-67 antibodies. Ki-67 expression was determined by light microscopy. Ki-67 expression was inhibited 25% in the organotypic culture treated with 9-cis retinoic acid and 32% in the culture treated with all-frans retinoic acid. Previous data demonstrated a 45% and 44% inhibition of EGF-R expression and a 49% and 63% inhibition of growth, respectively. The inhibition of Ki-67 expression by retinoids correlates with inhibition of EGF-R expression and growth as determined by a Pearson correlation (R = 0.88). Inhibition of Ki-67 and EGF-R demonstrates quantifiable effects of retinoids at both the membrane receptor and nuclear protein levels in our organotypic culture model.