Abstract

In these experiments, we tested the hypothesis that inhibition of the estrogen receptor (ER) with Tamoxifen and activation of PPARγ with fish oil (FO) rich in omega-3 (n-3; known PPAR agonists) inhibit the development of hormone-independent breast cancer in view of the known crosstalk between the ER and PPARγ pathways. We selected the polyoma middle T transgenic mouse model, since in this system the development of ER- tumors is preceded by ER positive preneoplastic lesions. Tamoxifen admixed with a 20% corn oil (CO) modified AIN-76A diet delayed mammary carcinogenesis and inhibited tumor multiplicity, volume, and weight in a dose-dependent (1, 10, and 100 ppm) fashion. Administration of increasing concentrations of FO in the diet (5%, 10%, and 17%) did not affect any of the tumor parameters. Combined administration of different doses of Tamoxifen and FO delayed carcinogenesis and suppressed tumor multiplicity and volume to the same extent as Tamoxifen alone. Mice fed 10% FO exhibited the expected increase in n-3/n-6 ratio in plasma and tumor based on diet analysis. Further increase in the n-3/n-6 ratio was not observed in mice fed the 17% FO diet. FO reduced tissue levels of arachidonic acid and its metabolite PGF-2α. Our results support the role of ER expression by preneoplastic lesions in the development of hormone-independent tumors and consequently the importance of including ER targeting in combination with mechanistically based novel chemopreventive agents.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalHormones and Cancer
Volume2
Issue number4
DOIs
StatePublished - Aug 1 2011

Fingerprint

Fish Oils
Tamoxifen
Estrogen Receptors
Transgenic Mice
Carcinogenesis
Breast
Peroxisome Proliferator-Activated Receptors
Tumor Burden
Diet
Neoplasms
Hormones
Corn Oil
Prostaglandins F
Arachidonic Acid
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

Cite this

Manni, Andrea ; Xu, Haifang ; Washington, Sharlene ; Aliaga, Cesar ; Das, Arunangshu ; Cooper, Timothy ; Richie, John P. ; Prokopczyk, Bogdan ; Calcagnotto, Ana ; Trushin, Neil ; Van den Heuvel, John P. ; Hamilton, Christopher ; Demers, Laurence M. ; Liao, Jason ; Verderame, Michael F. ; El-Bayoumy, Karam. / The Effects of Tamoxifen and Fish Oil on Mammary Carcinogenesis in Polyoma Middle T Transgenic Mice. In: Hormones and Cancer. 2011 ; Vol. 2, No. 4. pp. 249-259.
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abstract = "In these experiments, we tested the hypothesis that inhibition of the estrogen receptor (ER) with Tamoxifen and activation of PPARγ with fish oil (FO) rich in omega-3 (n-3; known PPAR agonists) inhibit the development of hormone-independent breast cancer in view of the known crosstalk between the ER and PPARγ pathways. We selected the polyoma middle T transgenic mouse model, since in this system the development of ER- tumors is preceded by ER positive preneoplastic lesions. Tamoxifen admixed with a 20{\%} corn oil (CO) modified AIN-76A diet delayed mammary carcinogenesis and inhibited tumor multiplicity, volume, and weight in a dose-dependent (1, 10, and 100 ppm) fashion. Administration of increasing concentrations of FO in the diet (5{\%}, 10{\%}, and 17{\%}) did not affect any of the tumor parameters. Combined administration of different doses of Tamoxifen and FO delayed carcinogenesis and suppressed tumor multiplicity and volume to the same extent as Tamoxifen alone. Mice fed 10{\%} FO exhibited the expected increase in n-3/n-6 ratio in plasma and tumor based on diet analysis. Further increase in the n-3/n-6 ratio was not observed in mice fed the 17{\%} FO diet. FO reduced tissue levels of arachidonic acid and its metabolite PGF-2α. Our results support the role of ER expression by preneoplastic lesions in the development of hormone-independent tumors and consequently the importance of including ER targeting in combination with mechanistically based novel chemopreventive agents.",
author = "Andrea Manni and Haifang Xu and Sharlene Washington and Cesar Aliaga and Arunangshu Das and Timothy Cooper and Richie, {John P.} and Bogdan Prokopczyk and Ana Calcagnotto and Neil Trushin and {Van den Heuvel}, {John P.} and Christopher Hamilton and Demers, {Laurence M.} and Jason Liao and Verderame, {Michael F.} and Karam El-Bayoumy",
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The Effects of Tamoxifen and Fish Oil on Mammary Carcinogenesis in Polyoma Middle T Transgenic Mice. / Manni, Andrea; Xu, Haifang; Washington, Sharlene; Aliaga, Cesar; Das, Arunangshu; Cooper, Timothy; Richie, John P.; Prokopczyk, Bogdan; Calcagnotto, Ana; Trushin, Neil; Van den Heuvel, John P.; Hamilton, Christopher; Demers, Laurence M.; Liao, Jason; Verderame, Michael F.; El-Bayoumy, Karam.

In: Hormones and Cancer, Vol. 2, No. 4, 01.08.2011, p. 249-259.

Research output: Contribution to journalArticle

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T1 - The Effects of Tamoxifen and Fish Oil on Mammary Carcinogenesis in Polyoma Middle T Transgenic Mice

AU - Manni, Andrea

AU - Xu, Haifang

AU - Washington, Sharlene

AU - Aliaga, Cesar

AU - Das, Arunangshu

AU - Cooper, Timothy

AU - Richie, John P.

AU - Prokopczyk, Bogdan

AU - Calcagnotto, Ana

AU - Trushin, Neil

AU - Van den Heuvel, John P.

AU - Hamilton, Christopher

AU - Demers, Laurence M.

AU - Liao, Jason

AU - Verderame, Michael F.

AU - El-Bayoumy, Karam

PY - 2011/8/1

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N2 - In these experiments, we tested the hypothesis that inhibition of the estrogen receptor (ER) with Tamoxifen and activation of PPARγ with fish oil (FO) rich in omega-3 (n-3; known PPAR agonists) inhibit the development of hormone-independent breast cancer in view of the known crosstalk between the ER and PPARγ pathways. We selected the polyoma middle T transgenic mouse model, since in this system the development of ER- tumors is preceded by ER positive preneoplastic lesions. Tamoxifen admixed with a 20% corn oil (CO) modified AIN-76A diet delayed mammary carcinogenesis and inhibited tumor multiplicity, volume, and weight in a dose-dependent (1, 10, and 100 ppm) fashion. Administration of increasing concentrations of FO in the diet (5%, 10%, and 17%) did not affect any of the tumor parameters. Combined administration of different doses of Tamoxifen and FO delayed carcinogenesis and suppressed tumor multiplicity and volume to the same extent as Tamoxifen alone. Mice fed 10% FO exhibited the expected increase in n-3/n-6 ratio in plasma and tumor based on diet analysis. Further increase in the n-3/n-6 ratio was not observed in mice fed the 17% FO diet. FO reduced tissue levels of arachidonic acid and its metabolite PGF-2α. Our results support the role of ER expression by preneoplastic lesions in the development of hormone-independent tumors and consequently the importance of including ER targeting in combination with mechanistically based novel chemopreventive agents.

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