Abstract
cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2′-deoxycytidine (BAC)/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 indnced TFPI-2 in cancer eels 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-mediaied 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 UDAC 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2386-2397 |
| Number of pages | 12 |
| Journal | Oncogene |
| Volume | 24 |
| Issue number | 14 |
| DOIs | |
| State | Published - Mar 31 2005 |
| Externally published | Yes |
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Keywords
- 5-aza 2′-deoxycytidine
- Depsipeptide FK228
- Esophageal cancer
- Lung cancer
- TFPI-2
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Sequential 5-Aza 2′-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells. / Steiner, Federico A.; Hong, Julie A.; Fischette, Maria R.; Beer, David G.; Guo, Zong Sheng; Chen, G. Aaron; Weiser, Todd S.; Kassis, Edmund S.; Nguyen, Dao; Lee, Sunmin; Trepel, Jane B.; Schrump, David S.
In: Oncogene, Vol. 24, No. 14, 31.03.2005, p. 2386-2397.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sequential 5-Aza 2′-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells
AU - Steiner, Federico A.
AU - Hong, Julie A.
AU - Fischette, Maria R.
AU - Beer, David G.
AU - Guo, Zong Sheng
AU - Chen, G. Aaron
AU - Weiser, Todd S.
AU - Kassis, Edmund S.
AU - Nguyen, Dao
AU - Lee, Sunmin
AU - Trepel, Jane B.
AU - Schrump, David S.
PY - 2005/3/31
Y1 - 2005/3/31
N2 - cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2′-deoxycytidine (BAC)/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 indnced TFPI-2 in cancer eels 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-mediaied 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 UDAC 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.
AB - cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2′-deoxycytidine (BAC)/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 indnced TFPI-2 in cancer eels 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-mediaied 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 UDAC 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.
KW - 5-aza 2′-deoxycytidine
KW - Depsipeptide FK228
KW - Esophageal cancer
KW - Lung cancer
KW - TFPI-2
UR - http://www.scopus.com/inward/record.url?scp=20144388727&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144388727&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208376
DO - 10.1038/sj.onc.1208376
M3 - Article
C2 - 15735751
AN - SCOPUS:20144388727
VL - 24
SP - 2386
EP - 2397
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 14
ER -