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Differential gene expression in ERα-positive and ERα-negative breast cancer cells upon leptin stimulation

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Abstract

In postmenopausal women, adipositas represents a serious risk factor for cancer development and progression. White adipose tissue secretes the 16 kDa hormone leptin which plays a key role in the regulation of appetite and metabolism. An increasing number of reports indicate that leptin also interferes with signal transduction pathways implicated in the development of breast cancer. In our previous study, we identified the estrogen receptor alpha (ERα) as a relevant enhancer of leptin-induced signal transduction leading to transactivation of signal transducer and activator of transcription 3 (Stat3). The purpose of this study is the investigation of specific target gene expression in response to leptin-mediated Stat3 signaling. We performed a comprehensive microarray analysis of ERα-positive and ERα-negative MDA-MB-231 cells upon leptin treatment and identified 49 genes which showed a significant ERα-dependent regulation in leptin-treated MDA-MB-231 cells. There was no intersection with genes which were merely up- or downregulated by ERα expression and only 9 and 11 genes overlapping targets which were regulated by leptin stimulation either in ERα-expressing or ERα-negative MDA-MB-231 cells, respectively. To demonstrate the specificity, expression of three target genes was validated by quantitative real-time PCR. In conclusion, these data imply that leptin can induce a different set of target genes dependent on ERα expression, which might contribute to the development and progression of cancer diseases.

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Abbreviations

ERα:

Estrogen receptor alpha

Ob-RL:

Leptin receptor

Stat3:

Signal transducer and activator of transcription 3

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Acknowledgments

We thank Dr. Bernd Groner (Georg Speyer Haus, Frankfurt, Germany) for providing MDA-MB-231 cells.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Nadine A. Binai

    Present address: Biomolecular Mass Spectrometry & Proteomics Group, Utrecht University, Utrecht, The Netherlands

Authors and Affiliations

  1. Paul-Ehrlich-Institute, Langen, Germany

    Nadine A. Binai, Gert Carra, Johannes Löwer & Roswitha Löwer

  2. Division of Microbiology, Paris-Lodron University of Salzburg, Salzburg, Austria

    Silja Wessler

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Correspondence to Silja Wessler.

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Binai, N.A., Carra, G., Löwer, J. et al. Differential gene expression in ERα-positive and ERα-negative breast cancer cells upon leptin stimulation. Endocrine 44, 496–503 (2013). https://doi.org/10.1007/s12020-013-9897-y

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