Terminal Differentiation of Human Breast Cancer through PPARγ

Elisabetta Mueller; Pasha Sarraf; Peter Tontonoz; Ronald M. Evans; Katherine J. Martin; Ming Zhang; Christopher Fletcher; Samuel Singer; Bruce M. Spiegelman

doi:10.1016/S1097-2765(00)80047-7

Terminal Differentiation of Human Breast Cancer through PPARγ

Elisabetta Mueller, Pasha Sarraf, Peter Tontonoz, Ronald M. Evans, Katherine J. Martin, Ming Zhang, Christopher Fletcher, Samuel Singer, Bruce M. Spiegelman^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

794 Scopus citations

Abstract

We have previously demonstrated that PPARγ stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPARγ is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPARγ, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPARγ transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.

Original language	English (US)
Pages (from-to)	465-470
Number of pages	6
Journal	Molecular cell
Volume	1
Issue number	3
DOIs	https://doi.org/10.1016/S1097-2765(00)80047-7
State	Published - Feb 1998

Funding

We thank Dr. George Demetri for discussions throughout the course of this work. We are grateful to Dr. Donald Kufe for the Muc-1 probe. This work was supported by a grant from the National Institutes of Health (B. M. S., grant # 5R37 DK31405). R. M. E. is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S1097-2765(00)80047-7

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title = "Terminal Differentiation of Human Breast Cancer through PPARγ",

abstract = "We have previously demonstrated that PPARγ stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPARγ is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPARγ, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPARγ transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.",

author = "Elisabetta Mueller and Pasha Sarraf and Peter Tontonoz and Evans, {Ronald M.} and Martin, {Katherine J.} and Ming Zhang and Christopher Fletcher and Samuel Singer and Spiegelman, {Bruce M.}",

note = "Funding Information: We thank Dr. George Demetri for discussions throughout the course of this work. We are grateful to Dr. Donald Kufe for the Muc-1 probe. This work was supported by a grant from the National Institutes of Health (B. M. S., grant # 5R37 DK31405). R. M. E. is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies.",

year = "1998",

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doi = "10.1016/S1097-2765(00)80047-7",

language = "English (US)",

volume = "1",

pages = "465--470",

journal = "Molecular cell",

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T1 - Terminal Differentiation of Human Breast Cancer through PPARγ

AU - Mueller, Elisabetta

AU - Sarraf, Pasha

AU - Tontonoz, Peter

AU - Evans, Ronald M.

AU - Martin, Katherine J.

AU - Zhang, Ming

AU - Fletcher, Christopher

AU - Singer, Samuel

AU - Spiegelman, Bruce M.

N1 - Funding Information: We thank Dr. George Demetri for discussions throughout the course of this work. We are grateful to Dr. Donald Kufe for the Muc-1 probe. This work was supported by a grant from the National Institutes of Health (B. M. S., grant # 5R37 DK31405). R. M. E. is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies.

PY - 1998/2

Y1 - 1998/2

N2 - We have previously demonstrated that PPARγ stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPARγ is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPARγ, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPARγ transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.

AB - We have previously demonstrated that PPARγ stimulates the terminal differentiation of adipocyte precursors when activated by synthetic ligands, such as the antidiabetic thiazolidinedione (TZD) drugs. We show here that PPARγ is expressed at significant levels in human primary and metastatic breast adenocarcinomas. Ligand activation of this receptor in cultured breast cancer cells causes extensive lipid accumulation, changes in breast epithelial gene expression associated with a more differentiated, less malignant state, and a reduction in growth rate and clonogenic capacity of the cells. Inhibition of MAP kinase, shown previously to be a powerful negative regulator of PPARγ, improves the TZD ligand sensitivity of nonresponsive cells. These data suggest that the PPARγ transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells and thus may provide a novel, nontoxic therapy for human breast cancer.

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DO - 10.1016/S1097-2765(00)80047-7

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JO - Molecular cell

JF - Molecular cell

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ER -

Terminal Differentiation of Human Breast Cancer through PPARγ

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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