Oncogene, 2005-03, Vol.24 (14), p.2386-2397
2005
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- Autor(en) / Beteiligte
- Titel
- Sequential 5-Aza 2′-deoxycytidine depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells
- Ist Teil von
- Oncogene, 2005-03, Vol.24 (14), p.2386-2397
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2'-deoxycytidine (DAC)/depsipeptide FK228 (DP) exposure in order to identify translational end points for clinical trials evaluating these agents. In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduction known to diminish the malignant phenotype of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell lines established from thoracic malignancies. Sequential DAC/DP treatment induced TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state. Promoter methylation coincided with loss of TFPI-2 expression in a number of cancer lines. TFPI-2 promoter methylation was observed in one of five pulmonary adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer cells deficient for TFPI-2 expression in the absence of promoter methylation. In these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling and PKC signaling strengthens the preclinical rationale for sequential administration of DNA demethylating agents and HDAC inhibitors in cancer patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of treatment response in individuals receiving sequential DAC/DP infusions.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1208376Titel-ID: cdi_proquest_miscellaneous_67566827
- Format
- –
- Schlagworte
- Acetylation, Apoptosis, Azacitidine - analogs & derivatives, Azacitidine - pharmacology, Base Sequence, Biological and medical sciences, Cancer, Cancer research, Cell cycle, Cell Line, Tumor, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Chromatin remodeling, Clinical trials, Coagulation factors, Cytotoxicity, Depsipeptides - pharmacology, DNA methylation, DNA microarrays, DNA Primers, Epigenetics, Esophageal cancer, Esophageal Neoplasms - metabolism, Esophageal Neoplasms - pathology, Esophagus, Fundamental and applied biological sciences. Psychology, Gastroenterology. Liver. Pancreas. Abdomen, Gene expression, Glycoproteins - genetics, Histone deacetylase, Histones, Humans, Kinases, Lung cancer, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Medical research, Medical sciences, Molecular and cellular biology, Oncology, Phenotypes, Pneumology, Protein kinase C, Proteins, Signal transduction, Surgery, Thorax, Tissue factor, Tumors, Tumors of the respiratory system and mediastinum