A Newly Characterized Human Endometrial Adenocarcinoma Cell Line (CAC-1) Differentiates in Response to Retinoic Acid Treatment

A new cell line of poorly differentiated human endometrial adenocarcinoma cells termed “CAC-1” cells has been established. These cells are epithelial, as indicated by positive cytokeratin and negative vimentin staining. They are rounded and possess a high nuclear-to-cytoplasmic ratio, desmosomes, surface microvilli, intercelular lumens, and pleomorphic nuclei containing multiple nucleoli. These cells have been in long-term culture for 2 years. Our previous studies demonstrated that moderately differentiated (RL95-2) cells differentiated in response to retinoic acid treatment, illustrated by their reorganization of actin filaments and cell enlargement (Carter et al., 1996; Anticancer Res.16, 17–24). CAC-1 cells exhibited a similar response because they also organized actin filaments and enlarged in response to retinoic acid treatment. Concurrently, retinoic acid treatment caused a 40% decrease in cell detachment in an in vitro detachment assay compared to controls. A slight lag in cell growth was observed when CAC-1 cells were treated with 1 μM 13-cis or all-trans retinoic acid during a 12-day growth curve. In addition, we examined the effects of retinoic acid on protein kinase C-α (PKC-α) and myristoylated alanine-rich C-kinase substrate (MARCKS). Treatment with retinoic acid caused cytoplasmic PKC-α to increase concomitant with a decrease in PKC-α in the membrane. In contrast, MARCKS increased in the membrane in response to retinoic acid treatment. These data indicate that retinoid treatment causes inactivation of PKC-α, allowing MARCKS to relocalize to the membrane, where it can cross-link actin filaments. CAC-1 cells represent an ideal model for investigating the effects of retinoids on differentiation induction concomitant with actin reorganization.