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Thromb Haemost 2005; 94(02): 444-453
DOI: 10.1160/TH05-01-0066
Cellular Proteolysis and Oncology
Schattauer GmbH

Tissue factor is regulated by epidermal growth factor in normal and malignant human endometrial epithelial cells

Sumie Kato
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
2   Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
,
Mauricio Pinto
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Andrés Carvajal
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Natalia Espinoza
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Carolina Monsó
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Loreto Bravo
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Manuel Villalon
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
,
Mauricio Cuello
2   Departamento de Obstetricia y Ginecologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
,
Andrew F. Quest
3   Centro FONDAP de Estudios Moleculares de la Celula (CEMC), Programa de Biologia Celular y Molecular, Universidad de Chile, Santiago, Chile
,
Akihiko Suenaga
4   Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, United Kingdom
,
Jan J. Brosens
4   Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, United Kingdom
,
Gareth I. Owen
1   Departamento de Endocrinología, Facultad de Ciencias Biológicas
› Author AffiliationsFinancial support: This work was supported by grant 1020715 (GIO), 1020675 (MC) and 15010006 (AFQ) from the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) and The Wellcome Trust International Collaboration Grants GR071469 (GIO) and WT0649IT/Z/01/Z (AFQ).
Further Information

Publication History

Received: 26 January 2005

Accepted after major revision: 22 May 2005

Publication Date:
05 December 2017 (online)

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Summary

Tissue Factor (TF), the initiator of the extrinsic coagulation cascade, is overexpressed in a variety of cancers. TF is also expressed in normal human endometrium but little is known about its expression or regulation in endometrial cancer. We demonstrate herein that TF is expressed in the endometrial adenocarcinoma cell line Ishikawa. Furthermore, epidermal growth factor (EGF) induces a rapid and sustained increase in TF expression. Estradiol and progesterone had no effect on basal or EGF-induced TF expression in Ishikawa cells. In contrast to the pronounced and sustained upregulation at the protein level,EGF treatment elicited only a modest and transient increase in TF mRNA levels. This activity corresponded to the response observed from an exogenous TF promoter construct. However, the induction of TF was abrogated by cycloheximide as well as actinomycin-D, inhibitors or protein- and mRNA-synthesis, re-spectively, demonstrating that EGF mediates its effect through activation of the TF gene. Fractionation experiments showed that EGF increases TF presence in caveolin-1 containing membrane fractions. Coagulation and invasion assays were used to explore the physiological implications of TF regulation. The results demonstrate that EGF-mediated induction of TF increases the procoagulant activity and invasive potential of Ishikawa cells. Furthermore, immunocytochemistry confirmed that TF is regulated by EGF in primary cultures of normal endometrial epithelial cells and malignant tumor cells. In conclusion, EGF-mediated upregulation ofTF results in accumulation of this glycoprotein in caveolae-like membrane fractions and increased coagulative and invasive potential. Our results suggest that TF may play an integral role in endometrial carcinogenesis.

Keywords

Endometrium - Ishikawa - coagulation - invasion - caveolin
 

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