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TMEFF2 is an androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cells

Oncogene volume 21, pages 4739–4746 (2002)Cite this article

Abstract

We have identified a gene that is highly expressed in the androgen-dependent prostate cancer cell line, LNCaP. Sequence analysis revealed that it was identical to a recently cloned gene designated TMEFF2, which encodes a transmembrane protein containing an epidermal growth factor (EGF)-like motif and two follistatin domains. This gene was highly expressed only in primary samples of normal prostate and prostate cancer as well as normal brain. Expression of the gene was controlled by androgen as shown by dihydrotestosterone markedly increasing TMEFF2 expression in LNCaP cells. Also, androgen-dependent human prostate cancer xenografts (CWR22) expressed high levels of TMEFF2 and these levels markedly decreased by day 10 after castration of the mice. Furthermore, a large number of androgen-dependent xenografts (CWR22, LuCaP-35, LAPC-4AD, LAPC-9AD) exhibited higher levels of TMEFF2 mRNA than androgen-independent xenografts (CWR22R, LAPC-3AI, LAPC-4AI, LAPC-9AI). Ectopic expression of TMEFF2 in DU145 and PC3 cells resulted in their prominent inhibition of growth. Taken together, the results demonstrate that TMEFF2 is a androgen-regulated gene, which can suppress growth of prostate cancer cells and our xenograft data show that escape of prostate cancer cells from androgen modulation causes them to decrease their expression of this gene, which may result in their more malignant behavior.

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Acknowledgements

This work was supported by National Institutes of Health Grant CA26038-20, Aron Eschman Fund, Parker Hughes Fund, C. and H. Koeffler Fund, Ko-So Foundation and Israel Humanitarian Fund. HP Koeffler is the holder of the Mark Goodson Chair in Oncology and is a member of the Jonnson Cancer Center.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, 90048, California, CA, USA

    Sigal Gery, David B Agus & H Phillip Koeffler

  2. Department of Medicine, UCLA School of Medicine, Los Angeles, 90095, California, CA, USA

    Charles L Sawyers

  3. Department of Pathology, Center for the Health Science, UCLA School of Medicine, Los Angeles, 90095, California, CA, USA

    Jonathan W Said

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  1. Sigal Gery
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Correspondence to Sigal Gery.

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Gery, S., Sawyers, C., Agus, D. et al. TMEFF2 is an androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cells. Oncogene 21, 4739–4746 (2002). https://doi.org/10.1038/sj.onc.1205142

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