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TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis.
Davidsen, M L; Würtz, S Ø; Rømer, M U; Sørensen, N M; Johansen, S K; Christensen, I J; Larsen, J K; Offenberg, H; Brünner, N; Lademann, U.
Afiliação
  • Davidsen ML; Department of Veterinary Pathobiology, The Royal Veterinary and Agricultural University, Ridebanevej 9, DK-1870 Frederiksberg C, Denmark.
Br J Cancer ; 95(8): 1114-20, 2006 Oct 23.
Article em En | MEDLINE | ID: mdl-17047657
Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of four inhibitors of the matrix metalloproteinases, which are capable of degrading most components of the extracellular matrix. However, in recent years, TIMP-1 has been recognised as a multifunctional protein, playing a complex role in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells and their genetically identical wild-type controls. For future studies, this cell system can be used to uncover the mechanisms and signalling pathways involved in the TIMP-1-mediated inhibition of apoptosis as well as to investigate the possibility of using TIMP-1 inhibitors to optimise the effect of conventional chemotherapy.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apoptose / Inibidor Tecidual de Metaloproteinase-1 / Antineoplásicos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Br J Cancer Ano de publicação: 2006 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apoptose / Inibidor Tecidual de Metaloproteinase-1 / Antineoplásicos Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Br J Cancer Ano de publicação: 2006 Tipo de documento: Article