title: Stimulation of CEACAM1 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore A23187 in endometrial carcinoma cells.
abstract: Downregulation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM1), a cell adhesion molecule with tumor suppressing properties has been observed in a high percentage of carcinomas of the endometrium and other malignancies. The mechanisms for the dysregulation and the role of hormones and cytokines on the expression of CEACAM1 in endometrial carcinomas is unknown. We therefore studied the effect of estradiol, medroxyprogesterone acetate (MPA), RU486, gamma-interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore A23187 on the expression in the non-expressing endometrial tumor cell lines Hec1B and Skut1B, respectively. No induction of CEACAM1 expression was observed in Hec1B endometrial adenocarcinoma cells in response to hormones and cytokines whereas treatment with TPA and calcium ionophore A23187 resulted in the strong expression of endogenous CEACAM1 on the mRNA and protein levels. In contrast, no induction of CEACAM1 expression was observed in endometrial mixed mesenchymal Skut1B cells. Studies of other members of the CEACAM family revealed that the re-expression in Hec1B carcinoma cells is restricted to CEACAM1 suggesting a cell type-specific and cell type-independent mechanism of CEACAM1 activation via the protein kinase C (PKC) pathway. Induction of CEACAM1 expression was dependent on protein kinase C protein synthesis and luciferase reporter assays with CEACAM1 promoter constructs demonstrated that the re-expression of CEACAM1 is regulated at the transcriptional level. This is the first report demonstrating that activators of PKC are able to specifically induce the expression of CEACAM1 in human carcinoma cells and our findings may provide a basis for the therapeutic inhibition of tumor growth in malignancies in which CEACAM1 is downregulated.
authors.affiliation: Department of Pathology, University Clinic Hamburg-Eppendorf, Germany. j.briese@uke.uni-hamburg.de
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Bamberger
authors.forename: Juliane
authors.initials: J
authors.lastname: Briese
authors.forename: Julica
authors.initials: J
authors.lastname: Götze
authors.forename: Insa
authors.initials: I
authors.lastname: Erdmann
authors.forename: Heinrich M
authors.initials: HM
authors.lastname: Schulte
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.forename: Peter
authors.initials: P
authors.lastname: Nollau
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis*; D000001:Calcimycin / Q000494:pharmacology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D004958:Estradiol / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D006727:Hormone Antagonists; D010703:Phorbol Esters; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D000001:Calcimycin; D004958:Estradiol; D007371:Interferon-gamma; D017258:Medroxyprogesterone Acetate; D011493:Protein Kinase C