Tumor necrosis factor α induces p53 up-regulated modulator of apoptosis expression in colorectal cancer cell lines

Danielle M. Pastor, Rosalyn Irby, Lisa Poritz

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PURPOSE: Inflammatory bowel disease (IBD)-associated colorectal carcinogenesis involves dysregulation of multiple cellular pathways, including p53 signaling and cytokine action. The purpose of the current study was to evaluate the effects of tumor necrosis factor α (TNF-α) on p53 and p53 up-regulated modulator of apoptosis (PUMA), a downstream effector of p53 in the apoptotic pathway in colorectal cancer cells. METHODS: The cell lines HT29 (which express mutant p53) and HCT116 (which express wild-type p53) were treated with TNF-α (0, 50,100, or 500 ng/mL) for 1,12, 24, or 48 hours. Protein expression and subcellular localization of p53 and PUMA were determined by immunoblot and immunofluorescence. Changes in p53 and PUMA mRNA expression were determined by quantitative real time polymerase chain reaction. RESULTS: Nuclear p53 expression was increased in TNF- α-treated HT29 cells; in contrast, expression was decreased or minimally changed in TNF-α-treated HCT116 cells, as determined by immunoblot and immunofluorescence. At 24 hours, p53 mRNA transcript levels were minimally increased in HT29 cells, whereas PUMA increased 34-fold. CONCLUSIONS: TNF-α increased nuclear p53 expression in HT29 cells, which express p53 mutation, but not in HCT116 cells, which are wild type for p53. In addition, TNF-α markedly up-regulated PUMA mRNA levels in HT29 cells. Our findings suggest that TNF-α may be a factor in carcinogenesis in IBD in cells carrying a p53 mutation.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalDiseases of the colon and rectum
Volume53
Issue number3
DOIs
StatePublished - Mar 1 2010

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Colorectal Neoplasms
Tumor Necrosis Factor-alpha
HT29 Cells
Apoptosis
Cell Line
HCT116 Cells
Inflammatory Bowel Diseases
Messenger RNA
Fluorescent Antibody Technique
Carcinogenesis
Mutation
Real-Time Polymerase Chain Reaction
Cytokines
Proteins

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

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title = "Tumor necrosis factor α induces p53 up-regulated modulator of apoptosis expression in colorectal cancer cell lines",
abstract = "PURPOSE: Inflammatory bowel disease (IBD)-associated colorectal carcinogenesis involves dysregulation of multiple cellular pathways, including p53 signaling and cytokine action. The purpose of the current study was to evaluate the effects of tumor necrosis factor α (TNF-α) on p53 and p53 up-regulated modulator of apoptosis (PUMA), a downstream effector of p53 in the apoptotic pathway in colorectal cancer cells. METHODS: The cell lines HT29 (which express mutant p53) and HCT116 (which express wild-type p53) were treated with TNF-α (0, 50,100, or 500 ng/mL) for 1,12, 24, or 48 hours. Protein expression and subcellular localization of p53 and PUMA were determined by immunoblot and immunofluorescence. Changes in p53 and PUMA mRNA expression were determined by quantitative real time polymerase chain reaction. RESULTS: Nuclear p53 expression was increased in TNF- α-treated HT29 cells; in contrast, expression was decreased or minimally changed in TNF-α-treated HCT116 cells, as determined by immunoblot and immunofluorescence. At 24 hours, p53 mRNA transcript levels were minimally increased in HT29 cells, whereas PUMA increased 34-fold. CONCLUSIONS: TNF-α increased nuclear p53 expression in HT29 cells, which express p53 mutation, but not in HCT116 cells, which are wild type for p53. In addition, TNF-α markedly up-regulated PUMA mRNA levels in HT29 cells. Our findings suggest that TNF-α may be a factor in carcinogenesis in IBD in cells carrying a p53 mutation.",
author = "Pastor, {Danielle M.} and Rosalyn Irby and Lisa Poritz",
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Tumor necrosis factor α induces p53 up-regulated modulator of apoptosis expression in colorectal cancer cell lines. / Pastor, Danielle M.; Irby, Rosalyn; Poritz, Lisa.

In: Diseases of the colon and rectum, Vol. 53, No. 3, 01.03.2010, p. 257-263.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tumor necrosis factor α induces p53 up-regulated modulator of apoptosis expression in colorectal cancer cell lines

AU - Pastor, Danielle M.

AU - Irby, Rosalyn

AU - Poritz, Lisa

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N2 - PURPOSE: Inflammatory bowel disease (IBD)-associated colorectal carcinogenesis involves dysregulation of multiple cellular pathways, including p53 signaling and cytokine action. The purpose of the current study was to evaluate the effects of tumor necrosis factor α (TNF-α) on p53 and p53 up-regulated modulator of apoptosis (PUMA), a downstream effector of p53 in the apoptotic pathway in colorectal cancer cells. METHODS: The cell lines HT29 (which express mutant p53) and HCT116 (which express wild-type p53) were treated with TNF-α (0, 50,100, or 500 ng/mL) for 1,12, 24, or 48 hours. Protein expression and subcellular localization of p53 and PUMA were determined by immunoblot and immunofluorescence. Changes in p53 and PUMA mRNA expression were determined by quantitative real time polymerase chain reaction. RESULTS: Nuclear p53 expression was increased in TNF- α-treated HT29 cells; in contrast, expression was decreased or minimally changed in TNF-α-treated HCT116 cells, as determined by immunoblot and immunofluorescence. At 24 hours, p53 mRNA transcript levels were minimally increased in HT29 cells, whereas PUMA increased 34-fold. CONCLUSIONS: TNF-α increased nuclear p53 expression in HT29 cells, which express p53 mutation, but not in HCT116 cells, which are wild type for p53. In addition, TNF-α markedly up-regulated PUMA mRNA levels in HT29 cells. Our findings suggest that TNF-α may be a factor in carcinogenesis in IBD in cells carrying a p53 mutation.

AB - PURPOSE: Inflammatory bowel disease (IBD)-associated colorectal carcinogenesis involves dysregulation of multiple cellular pathways, including p53 signaling and cytokine action. The purpose of the current study was to evaluate the effects of tumor necrosis factor α (TNF-α) on p53 and p53 up-regulated modulator of apoptosis (PUMA), a downstream effector of p53 in the apoptotic pathway in colorectal cancer cells. METHODS: The cell lines HT29 (which express mutant p53) and HCT116 (which express wild-type p53) were treated with TNF-α (0, 50,100, or 500 ng/mL) for 1,12, 24, or 48 hours. Protein expression and subcellular localization of p53 and PUMA were determined by immunoblot and immunofluorescence. Changes in p53 and PUMA mRNA expression were determined by quantitative real time polymerase chain reaction. RESULTS: Nuclear p53 expression was increased in TNF- α-treated HT29 cells; in contrast, expression was decreased or minimally changed in TNF-α-treated HCT116 cells, as determined by immunoblot and immunofluorescence. At 24 hours, p53 mRNA transcript levels were minimally increased in HT29 cells, whereas PUMA increased 34-fold. CONCLUSIONS: TNF-α increased nuclear p53 expression in HT29 cells, which express p53 mutation, but not in HCT116 cells, which are wild type for p53. In addition, TNF-α markedly up-regulated PUMA mRNA levels in HT29 cells. Our findings suggest that TNF-α may be a factor in carcinogenesis in IBD in cells carrying a p53 mutation.

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