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Overexpression of PPARγ can down-regulate Skp2 expression in MDA-MB-231 breast tumor cells

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Abstract

Skp2 is frequent amplified and overexpressed in breast cancer, making it a potential molecular target for cancer therapy. The objective of this study was to examine the effect of PPARγ overexpression on Skp2 expression in breast cancer cell lines. First, we investigated the role of PPARγ and Skp2 in human breast cancer progression. Immunohistochemical analysis of 70 specimens on formalin-fixed paraffin sections was performed. Furthermore in vitro, Western blot analysis was used to study the relationship between PPARγ and Skp2. We found that the expression of PPARγ and Skp2 expression was inverse correlation whether in vivo or in vitro. In addition, PPARγ overexpression can down-regulate the expression of Skp2 mRNA and protein in breast cancer cells. PPARγ overexpression decreased breast cancer cell proliferation and induced spontaneous apoptosis even in the absence of exogenous ligand. These PPARγ-overexpressing cells were dramatically more sensitive to PPARγ ligand-induced apoptosis compared with parental or Myc-control transfected cells. Overexpressing of Skp2 partially reversed PPARγ’s pro-apoptotic and anti-proliferative abilities. These results suggested that PPARγ’s pro-apoptotic and anti-proliferative abilities appear to be triggered at least in part by the modulation of Skp2.

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Abbreviations

Skp2:

S-phase kinase-associated protein 2

PPARγ:

Peroxisome proliferator-activated receptor γ

Tro:

Troglitazone

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China (No. 30300099, No. 30770488, and No. 30870320); Natural Science Foundation of Jiangsu province (No. BK2009156, No. BK2009157, No. BK2009161); Health Department of Jiangsu Province (H200760) and Key Subject of Jiangsu Province (xk20070320).

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Authors and Affiliations

  1. Medical Laboratory Center, Affiliated Hospital of Nantong University, No. 20, Road Xisi, Nantong, Jiangsu, 226001, People’s Republic of China

    Jie Meng, Huoyan Ji & Huimin Wang

  2. Department of Breast Surgery, Maternal and Child Health Hospital of Wuxi City, Wuxi, 214002, People’s Republic of China

    Yun Ding, You Wang & Xiaowei Lu

  3. Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu, 226001, China

    Aiguo Shen, Meijuan Yan & Yonghua Liu

  4. Department of Pathology, Affliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, 226001, People’s Republic of China

    Fei He & Lin Zou

Authors
  1. Jie Meng
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  2. Yun Ding
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  3. Aiguo Shen
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  4. Meijuan Yan
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  5. Fei He
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  6. Huoyan Ji
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  7. Lin Zou
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  8. Yonghua Liu
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  9. You Wang
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  10. Xiaowei Lu
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  11. Huimin Wang
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Corresponding authors

Correspondence to Xiaowei Lu or Huimin Wang.

Additional information

Jie Meng and Yun Ding contributed equally to this work.

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11010_2010_570_MOESM1_ESM.tif

Information about the specificities of antibodies (×400). Immunostaining was performed using the PPARγ antibodies (a) or Skp2 antibodies (c) but not the secondary antibodies. On the other hand, Immunostaining was performed using normal rabbit IgG and the secondary antibodies (b, d). (TIFF 5709 kb)

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Meng, J., Ding, Y., Shen, A. et al. Overexpression of PPARγ can down-regulate Skp2 expression in MDA-MB-231 breast tumor cells. Mol Cell Biochem 345, 171–180 (2010). https://doi.org/10.1007/s11010-010-0570-y

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  • DOI: https://doi.org/10.1007/s11010-010-0570-y

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