Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1,N 11-diethylnorspermine

Edward Gabrielson, Ellen Tully, Amy Hacker, Anthony Pegg, Nancy E. Davidson, Robert A. Casero

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: The polyamine analogue, N1,N11- diethylnorspermine (DENSpm), is currently being evaluated in clinical trials for the treatment of solid tumors. The response of solid tumors to this drug has been associated with superinduction of the polyamine catabolic enzyme, spermine/spermidine N1-acetyltransferase (SSAT). Therefore, to estimate the response of breast cancers to DENSpm, we measured induction of SSAT in breast cancer explants treated in vitro with this polyamine analogue. Experimental design: Expression of SSAT protein was evaluated by immunohistochemistry in tissue explants from 38 invasive breast cancer tumors incubated in vitro in the presence (or absence) of DENSpm. In addition, SSAT enzymatic activity was measured in tissue explants from four tumors with high cellularity. Results: SSAT expression was significantly increased in 30 of 38 tumor samples treated with DENSpm compared to untreated controls. This induction of SSAT protein expression was found specifically in neoplastic cells of the treated samples, and was seen in all histologic patterns (ductal, lobular, and mucinous) of breast cancer examined. In tumor samples evaluated for changes in SSAT enzymatic activity, these changes correlated closely with changes in protein expression. Conclusions: Immunohistochemical staining for induction of SSAT correlates with measures of enzymatic activity in a small sample where measurements were possible and suggests that immunohistochemistry may be used for predicting response of breast cancers to DENSpm. A high proportion of breast cancers induced SSAT in response to DENSpm, supporting the continued consideration of this class of agents for treatment of breast cancer.

Original languageEnglish (US)
Pages (from-to)122-126
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume54
Issue number2
DOIs
StatePublished - Jan 1 2004

Fingerprint

Acetyltransferases
Spermidine
Spermine
Polyamines
Tissue
Breast Neoplasms
Tumors
Neoplasms
Immunohistochemistry
diamine N-acetyltransferase
Proteins
Design of experiments
Research Design
Clinical Trials
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Gabrielson, Edward ; Tully, Ellen ; Hacker, Amy ; Pegg, Anthony ; Davidson, Nancy E. ; Casero, Robert A. / Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1,N 11-diethylnorspermine. In: Cancer Chemotherapy and Pharmacology. 2004 ; Vol. 54, No. 2. pp. 122-126.
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abstract = "Purpose: The polyamine analogue, N1,N11- diethylnorspermine (DENSpm), is currently being evaluated in clinical trials for the treatment of solid tumors. The response of solid tumors to this drug has been associated with superinduction of the polyamine catabolic enzyme, spermine/spermidine N1-acetyltransferase (SSAT). Therefore, to estimate the response of breast cancers to DENSpm, we measured induction of SSAT in breast cancer explants treated in vitro with this polyamine analogue. Experimental design: Expression of SSAT protein was evaluated by immunohistochemistry in tissue explants from 38 invasive breast cancer tumors incubated in vitro in the presence (or absence) of DENSpm. In addition, SSAT enzymatic activity was measured in tissue explants from four tumors with high cellularity. Results: SSAT expression was significantly increased in 30 of 38 tumor samples treated with DENSpm compared to untreated controls. This induction of SSAT protein expression was found specifically in neoplastic cells of the treated samples, and was seen in all histologic patterns (ductal, lobular, and mucinous) of breast cancer examined. In tumor samples evaluated for changes in SSAT enzymatic activity, these changes correlated closely with changes in protein expression. Conclusions: Immunohistochemical staining for induction of SSAT correlates with measures of enzymatic activity in a small sample where measurements were possible and suggests that immunohistochemistry may be used for predicting response of breast cancers to DENSpm. A high proportion of breast cancers induced SSAT in response to DENSpm, supporting the continued consideration of this class of agents for treatment of breast cancer.",
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Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1,N 11-diethylnorspermine. / Gabrielson, Edward; Tully, Ellen; Hacker, Amy; Pegg, Anthony; Davidson, Nancy E.; Casero, Robert A.

In: Cancer Chemotherapy and Pharmacology, Vol. 54, No. 2, 01.01.2004, p. 122-126.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1,N 11-diethylnorspermine

AU - Gabrielson, Edward

AU - Tully, Ellen

AU - Hacker, Amy

AU - Pegg, Anthony

AU - Davidson, Nancy E.

AU - Casero, Robert A.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Purpose: The polyamine analogue, N1,N11- diethylnorspermine (DENSpm), is currently being evaluated in clinical trials for the treatment of solid tumors. The response of solid tumors to this drug has been associated with superinduction of the polyamine catabolic enzyme, spermine/spermidine N1-acetyltransferase (SSAT). Therefore, to estimate the response of breast cancers to DENSpm, we measured induction of SSAT in breast cancer explants treated in vitro with this polyamine analogue. Experimental design: Expression of SSAT protein was evaluated by immunohistochemistry in tissue explants from 38 invasive breast cancer tumors incubated in vitro in the presence (or absence) of DENSpm. In addition, SSAT enzymatic activity was measured in tissue explants from four tumors with high cellularity. Results: SSAT expression was significantly increased in 30 of 38 tumor samples treated with DENSpm compared to untreated controls. This induction of SSAT protein expression was found specifically in neoplastic cells of the treated samples, and was seen in all histologic patterns (ductal, lobular, and mucinous) of breast cancer examined. In tumor samples evaluated for changes in SSAT enzymatic activity, these changes correlated closely with changes in protein expression. Conclusions: Immunohistochemical staining for induction of SSAT correlates with measures of enzymatic activity in a small sample where measurements were possible and suggests that immunohistochemistry may be used for predicting response of breast cancers to DENSpm. A high proportion of breast cancers induced SSAT in response to DENSpm, supporting the continued consideration of this class of agents for treatment of breast cancer.

AB - Purpose: The polyamine analogue, N1,N11- diethylnorspermine (DENSpm), is currently being evaluated in clinical trials for the treatment of solid tumors. The response of solid tumors to this drug has been associated with superinduction of the polyamine catabolic enzyme, spermine/spermidine N1-acetyltransferase (SSAT). Therefore, to estimate the response of breast cancers to DENSpm, we measured induction of SSAT in breast cancer explants treated in vitro with this polyamine analogue. Experimental design: Expression of SSAT protein was evaluated by immunohistochemistry in tissue explants from 38 invasive breast cancer tumors incubated in vitro in the presence (or absence) of DENSpm. In addition, SSAT enzymatic activity was measured in tissue explants from four tumors with high cellularity. Results: SSAT expression was significantly increased in 30 of 38 tumor samples treated with DENSpm compared to untreated controls. This induction of SSAT protein expression was found specifically in neoplastic cells of the treated samples, and was seen in all histologic patterns (ductal, lobular, and mucinous) of breast cancer examined. In tumor samples evaluated for changes in SSAT enzymatic activity, these changes correlated closely with changes in protein expression. Conclusions: Immunohistochemical staining for induction of SSAT correlates with measures of enzymatic activity in a small sample where measurements were possible and suggests that immunohistochemistry may be used for predicting response of breast cancers to DENSpm. A high proportion of breast cancers induced SSAT in response to DENSpm, supporting the continued consideration of this class of agents for treatment of breast cancer.

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