Exp Clin Endocrinol Diabetes 2006; 114 - P10_130
DOI: 10.1055/s-2006-933015

Stimulation of CEACAM1 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and Calcium Ionophore A23187 in endometrial carcinoma cells and placental hybridoma cells

J Briese 1, T Heilmann 2, CM Bamberger 2, J Götze 3, I Erdmann 4, HM Schulte 4, C Wagener 3, P Nollau 3, AM Bamberger 1
  • 1University Clinic Hamburg-Eppendorf, Department of Pathology, Hamburg, Germany
  • 2University Clinic Hamburg-Eppendorf, Department of Medicine, Hamburg, Germany
  • 3University Clinic Hamburg-Eppendorf, Department of Clinical Chemistry, Hamburg, Germany
  • 4Endokrinologikum, Hamburg, Germany

Objectives: Up- and downregulation of CEACAM1, a cell adhesion molecule with tumor suppressing and stimulating properties has been observed in a high percentage of endometrial tumors as well as in the placenta. The mechanisms for the dysregulation and the role of hormones on the expression of CEACAM1 in endometrial tumors and in the placenta are unknown.

Methods: We investigated the effect of estradiol, medroxyprogesterone acetate (MPA), glucocorticoids, fosgolin, O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore A23187 on the expression of CEACAM1 and on the activity of transfected CEACAM1 promoter constructs in endometrial carcinoma cells Hec1B and Skut1B and the placental hybridoma cells ACI 81/88.

Results: No induction of CEACAM1 expression was observed in all cell lines in response to steroid hormones, while treatment with TPA and calcium ionophore A23187 resulted in an expression of endogenous CEACAM1 on the mRNA and protein levels in Hec1B cells and placenta cells. In contrast, no induction of expression was observed in endometrial mesenchymal Skut1B cells. Studies on other members of the CEACAM1 family revealed that the re-expression in Hec1B and ACI81/88 cells is restricted to CEACAM1 activation via the protein kinase C (PKC) pathway. The different response to TPA and calcium ionophore A23187 observed in all cells is probably due to cell type specific differences in the expression pattern of PKC isoforms and the activation of subsequent signaling pathways. Induction of CEACAM1 expression was dependent on the RNA and protein synthesis and luciferase reporter assays with CEACAM1 promoter constructs demonstrated that the re-expression of CEACAM1 is regulated on the transcriptional level.

Conclusion: This is the first report demonstrating that activators of PKC are able to specifically induce the expression of CEACAM1 in endometrial carcinoma cells and placenta cells and our findings may provide a basis for the therapeutic inhibition of tumor growth in malignancies in which CEACAM1 is dysregulated.