Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility

Yongzhi Cui, Keiko Miyoshi, Estefania Claudio, Ulrich K. Siebenlist, Frank J. Gonzalez, Jodi Flaws, Kay Uwe Wagner, Lothar Hennighausen

Research output: Contribution to journalArticle

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Abstract

The peroxisome proliferation-activated receptor gamma (PPARγ) is expressed in many cell types including mammary epithelium, ovary, macrophages, and B-and T-cells. PPARγ has an anti-proliferative effect in pre-adipocytes and mammary epithelial cells, and treatment with its ligands reduced the progression of carcinogen-induced mammary tumors in mice. Because PPARγ-null mice die in utero it has not been possible to study its role in development and tumorigenesis in vivo. To investigate whether PPARγ is required for the establishment and physiology of different cell types, a cellspecific deletion of the gene was carried out in mice using the Cre-loxP recombination system. We deleted the PPARγ gene in mammary epithelium using WAP-Cre transgenic mice and in epithelial cells, B- and T-cells, and ovary cells using MMTV-Cre mice. The presence of PPARγ was not required for functional development of the mammary gland during pregnancy and for the establishment of B- and T-cells. In addition, no increase in mammary tumors was observed. However, loss of the PPARγ gene in oocytes and granulosa cells resulted in impaired fertility. These mice have normal populations of follicles, they ovulate and develop corpora lutea. Although progesterone levels are decreased and implantation rates are reduced, the exact cause of the impaired fertility remains to be determined.

Original languageEnglish (US)
Pages (from-to)17830-17835
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number20
DOIs
StatePublished - May 17 2002

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Peroxisomes
T-cells
Fertility
Tumors
Breast
Genes
Neoplasms
Macrophages
Physiology
Carcinogens
Progesterone
T-Lymphocytes
Cells
Ovary
Ligands
Epithelium
Epithelial Cells
Breast Neoplasms
Cell Physiological Phenomena
Granulosa Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility. / Cui, Yongzhi; Miyoshi, Keiko; Claudio, Estefania; Siebenlist, Ulrich K.; Gonzalez, Frank J.; Flaws, Jodi; Wagner, Kay Uwe; Hennighausen, Lothar.

In: Journal of Biological Chemistry, Vol. 277, No. 20, 17.05.2002, p. 17830-17835.

Research output: Contribution to journalArticle

Cui, Yongzhi ; Miyoshi, Keiko ; Claudio, Estefania ; Siebenlist, Ulrich K. ; Gonzalez, Frank J. ; Flaws, Jodi ; Wagner, Kay Uwe ; Hennighausen, Lothar. / Loss of the peroxisome proliferation-activated receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 20. pp. 17830-17835.
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