Repressed PKC delta activation in glycodelin-expressing cells mediates resistance to phorbol ester and TGF beta

Autor: Riitta Koistinen, Laura Hautala, Hannu Koistinen
Přispěvatelé: Medicum, Department of Clinical Chemistry and Hematology
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
CARCINOMA
MIGRATION
Cellular differentiation
Endometrial carcinoma
PKC delta
UP-REGULATION
03 medical and health sciences
chemistry.chemical_compound
DOMAIN-CONTAINING PROTEIN-1
Downregulation and upregulation
Cell Movement
Transforming Growth Factor beta
TGF beta
Cell Line
Tumor
TGF beta signaling pathway
Cell differentiation
Humans
RNA
Small Interfering
PROTEIN-KINASE-C
PHOSPHORYLATION
Cell Shape
Protein kinase C
biology
Glycodelin
ENDOMETRIAL ADENOCARCINOMA CELLS
MAPK pathway
Cell Biology
Transforming growth factor beta
CANCER
Cell biology
Enzyme Activation
Protein Kinase C-delta
Phenotype
030104 developmental biology
DIFFERENTIATION
chemistry
Phorbol
biology.protein
Tetradecanoylphorbol Acetate
GROWTH
1182 Biochemistry
cell and molecular biology
Transforming growth factor
Popis: Glycodelin is a glycoprotein mainly expressed in well-differentiated epithelial cells in reproductive tissues. In normal secretory endometrium, the expression of glycodelin is abundant and regulated by progesterone. In hormone-related cancers glycodelin expression is associated with well-differentiated tumors. We have previously found that glycodelin drives epithelial differentiation of HEC-1B endometrial adenocarcinoma cells, resulting in reduced tumor growth in a preclinical mouse model. Here we show that glycodelin-transfected HEC-1B cells have repressed protein kinase C delta (PKC delta) activation, likely due to downregulation of PDKI, and are resistant to phenotypic change and enhanced migration induced by phorbo112-myristate 13-acetate (PMA). In control cells, which do not express glycodelin, the effects of PMA were abolished by using PKC6 and PDKI inhibitors, and knockdown of PKC delta, MEK1 and 2, or ERK1 and 2 by siRNAs. Similarly, transforming growth factor beta (TGF beta)-induced phenotypic change was only seen in control cells, not in glycodelin-producing cells, and it was mediated by PKC delta. Taken together, these results strongly suggest that PKC delta, via MAPI( pathway, is involved in the glycodelin-driven cell differentiation rendering the cells resistant to stimulation by PMA and TGF beta. (C) 2016 Elsevier Inc. All rights reserved.
Databáze: OpenAIRE
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