Abstract
Transforming growth factor-beta (TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear. In this study, TIEG1 was found to induce apoptosis in TGF-beta resistant cancer cells and concurrently enhanced gemcitabine chemosensitivity. Down-regulation of stathmin was noted to associate with TIEG1 expression, whilst ectopic overexpression of stathmin prevented TIEG1 mediated growth inhibition of tumor cells. Small interfering RNAs targeting stathmin inhibited pancreatic cancer cell growth. These suggest that stathmin is a downstream target of TIEG1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology
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Apoptosis*
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Blotting, Western
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Cell Proliferation / drug effects*
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Down-Regulation
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Drug Resistance, Neoplasm
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Early Growth Response Transcription Factors / physiology*
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Gemcitabine
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Humans
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Kruppel-Like Transcription Factors / physiology*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Ribonucleotide Reductases / antagonists & inhibitors
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Stathmin / metabolism*
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Transforming Growth Factor beta / metabolism
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Tumor Cells, Cultured
Substances
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Antimetabolites, Antineoplastic
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Early Growth Response Transcription Factors
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KLF10 protein, human
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Kruppel-Like Transcription Factors
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RNA, Messenger
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RNA, Small Interfering
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Stathmin
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Transforming Growth Factor beta
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Deoxycytidine
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Ribonucleotide Reductases
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Gemcitabine