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Basic Research

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer

Prostate Cancer and Prostatic Diseases volume 15, pages 339–345 (2012)Cite this article

Subjects

Abstract

Background:

We previously conducted a genome-wide linkage analysis of Japanese nuclear families affected with prostate cancer and showed that the susceptibility to prostate cancer was closely linked to D8S550 at 8p23. The role of farnesyl diphosphate farnesyltransferase (FDFT1), which is located under the peak marker D8S550 at 8p23, and squalene synthase, the enzyme encoded by FDFT1, in prostate cancer was studied.

Methods:

The association among common variants of FDFT1 with prostate cancer risk, the promoter activities of FDFT1 with different genotypes and the effects of inhibition of squalene synthase were studied, and the FDFT1 transcript levels of human prostate samples were quantified.

Results:

The A allele of rs2645429 was significantly associated with prostate cancer risk in a Japanese familial prostate cancer population. Rs2645429 was located in the promoter region of FDFT1, and the AA genotype showed significantly increased promoter activity. The knockdown of FDFT1 mRNA expression or squalene synthase inhibition led to a significant decrease in prostate cancer cell proliferation. Additionally, human prostate cancer specimens expressed significantly higher levels of FDFT1 mRNA compared with noncancerous specimens. Finally, aggressive cancers showed higher transcript levels.

Conclusions:

FDFT1 and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes.

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Acknowledgements

We thank Naomi Takase for providing excellent technical support. We are grateful to the following doctors for registering the patients with FPC analyzed in this study: Nobuaki Shimizu, Takanori Suzuki, Takeo Makino, Isao Kurosawa, Yasushige Matsuo, Jun Kuribara, Kazuhisa Saruki, Kazuhiko Okabe, Yukio Tomaru, Yoshimi Tamura, Tetsuo Sekihara, Toshiyuki Nakamura, Kohei Kurokawa, Tomoyuki Takei, Yoshio Ichinose, Susumu Jinbo, Tadatoshi Shinozaki, Mikio Kobayashi and Hidetoshi Yamanaka. This study was supported by a Grant-in-Aid for Scientific Research (B) from MEXT, Japan (Project number: 17390436, 20390419).

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Authors and Affiliations

  1. Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan

    Y Fukuma, H Matsui, H Koike, Y Sekine, N Ohtake, S Nakata, K Ito & K Suzuki

  2. Division of Cardiology, Department of Medicine, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA, USA

    I Shechter

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  1. Y Fukuma
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Correspondence to K Suzuki.

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Fukuma, Y., Matsui, H., Koike, H. et al. Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer. Prostate Cancer Prostatic Dis 15, 339–345 (2012). https://doi.org/10.1038/pcan.2012.14

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