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Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells

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Abstract

Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 μM sarcosine for 24 h resulted in a 58% increase of the HER2/neu mRNA level (P < 0.001) indicating that sarcosine effects HER2/neu expression on the level of transcription. Control experiments with alanine, an isomer of sarcosine, showed no significant effect on HER2/neu transcription. The upregulation of HER2/neu mRNA preceded the corresponding increment of the protein level after the 48-h exposure to sarcosine as shown by WB and confocal microscopy. Interestingly, sarcosine had no effect on the activated (phosphorylated) form of HER2/neu. No significant change in AR expression was observed after exposure to sarcosine. This is the first report indicating that sarcosine is involved in the regulation of the oncoprotein HER2/neu. Thus, sarcosine may induce prostate cancer progression by increased HER2/neu expression. However, detailed information on cellular mechanisms remains to be elucidated.

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Acknowledgments

We thank Majken Madvig Jansen (Cancer and Molecular Imaging Unit, Department of Clinical Biochemistry, Koege Hospital, Denmark) for expert technical assistance. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This work was sponsored by the Holger K. Christiansen Foundation, Denmark, Grant no. 74272 KB; Foundation of Region of Zealand, Denmark, Grant no. 1-01-83-0011-07. The contribution of JC and GKM to this work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Cancer and Molecular Imaging Unit, Research Division of Clinical Biochemistry, University of Copenhagen, Koege Hospital, 4600, Koege, Denmark

    Malin Dahl, Pierre Bouchelouche & Kirsten Bouchelouche

  2. Molecular Targeting Section, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Gabriela Kramer-Marek & Jacek Capala

  3. Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark

    Jørgen Nordling

  4. PET and Cyclotron Unit, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Kirsten Bouchelouche

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  1. Malin Dahl
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  2. Pierre Bouchelouche
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  3. Gabriela Kramer-Marek
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Correspondence to Malin Dahl.

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Dahl, M., Bouchelouche, P., Kramer-Marek, G. et al. Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells. Mol Biol Rep 38, 4237–4243 (2011). https://doi.org/10.1007/s11033-010-0442-2

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  • DOI: https://doi.org/10.1007/s11033-010-0442-2

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