the metalloproteinase ADAM-12 regulates bronchial epithelial cell proliferation and apoptosis.

[en] Objectives: The ADAMs (a disintegrin and metalloproteinase) enzymes compose a family of membrane-bound proteins characterized by their multi-domain structure and ADAM-12 expression is elevated in human non-small cell lung cancers. The aim of this study was to investigate the roles played by ADAM-12 in critical steps of bronchial cell transformation during carcinogenesis. Materials and methods: To assess the role of ADAM-12 in tumorigenicity, BEAS-2B cells were transfected with a plasmid encoding human full-length ADAM-12 cDNA, and then the effects of ADAM-12 overexpression on cell behaviour were explored. Treatment of clones with heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) neutralizing antibodies as well as an EGFR inhibitor allowed the dissection of mechanisms regulating cell proliferation and apoptosis. Results: Overexpression of ADAM-12 in BEAS-2B cells promoted cell proliferation. ADAM-12 overexpressing clones produced higher quantities of HB-EGF in their culture medium which may rely on membrane-bound HB-EGF shedding by ADAM-12. Targeting HB-EGF activity with a neutralizing antibody abrogated enhanced cell proliferation in the ADAM-12 overexpressing clones. In sharp contrast, targeting of amphiregulin, EGF or transforming growth factor-α failed to influence cell proliferation; moreover, ADAM-12 transfectants were resistant to etoposide-induced apoptosis and the use of a neutralizing antibody against HB-EGF activity restored rates of apoptosis to be similar to controls. Conclusions: ADAM-12 contributes to enhancing HB-EGF shedding from plasma membranes leading to increased cell proliferation and reduced apoptosis in this bronchial epithelial cell line.

Research center :

Giga-Cancer - ULiège

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Rocks, Natacha ^✱; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Estrella, C. ^✱

Paulissen, Geneviève ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Quesada Calvo, Florence ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Guéders, Maud ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Crahay, Céline

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement

Gosset, Ph

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Cataldo, Didier ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques

^✱ These authors have contributed equally to this work.

Language :

English

Title :

the metalloproteinase ADAM-12 regulates bronchial epithelial cell proliferation and apoptosis.

Publication date :

2008

Journal title :

Cell Proliferation

ISSN :

0960-7722

eISSN :

1365-2184

Publisher :

Blackwell Publishing, Oxford, United Kingdom

Volume :

Issue :

Pages :

988-1001

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 10 March 2009

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