Journal
EUROPEAN JOURNAL OF CANCER
Volume 57, Issue -, Pages 39-49Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2016.01.002
Keywords
ABHD2; Androgen receptor; Prostate cancer
Categories
Funding
- Grants of the PDIRECT
- Cell Innovation Program from the MEXT, Japan
- JSPS, Japan [4791675, 26861302, 15K15581, 15K15353, 15K10610]
- Research Grant of the 60th Anniversary Memorial Fund from Nihon University Medical Alumni Association
- Nihon University School of Medicine 50th Anniversary Fund Research Grant from Nihon University School of Medicine
- Young Researcher Promotion Grant from The Japanese Urological Association
- Program for Promotion of Fundamental Studies in Health Sciences, NIBIO, Japan
- Grants-in-Aid for Scientific Research [15K15581, 16K15496, 15K10610, 15K15353, 26293223, 26861302] Funding Source: KAKEN
Ask authors/readers for more resources
Background: The androgen receptor (AR) plays a key role in the development of prostate cancer. AR signalling mediates the expression of androgen-responsive genes, which are involved in prostate cancer development and progression. Our previous chromatin immunoprecipitation study showed that the region of abhydrolase domain containing 2 (ABHD2) includes a functional androgen receptor binding site. In this study, we demonstrated that ABHD2 is a novel androgen-responsive gene that is overexpressed in human prostate cancer tissues. Methods: The expression levels of ABHD2 in androgen-sensitive cells were evaluated by quantitative reverse transcription polymerase chain reaction and western-blot analyses. LNCaP and VCaP cells with ABHD2 overexpression or short interfering RNA (siRNA) knockdown were used for functional analyses. ABHD2 expression was examined in clinical samples of prostate cancer by immunohistochemistry. Results: We showed that ABHD2 expression is increased by androgen in LNCaP and VCaP cells. This androgen-induced ABHD2 expression was diminished by bicalutamide. While stable expression of ABHD2 affected the enhancement of LNCaP cell proliferation and migration, siRNA-mediated ABHD2 knockdown suppressed cell proliferation and migration. In addition, the siRNA treatment significantly repressed the tumour growth derived from LNCaP cells in athymic mice. Immunohistochemical analysis of ABHD2 expression in tumour specimens showed a positive correlation of ABHD2 immunoreactivity with high Gleason score and pathological N stage. Moreover, patients with high immunoreactivity of ABHD2 showed low cancer-specific survival rates and a resistance to docetaxel-based chemotherapy. Conclusion: ABHD2 is a novel androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy, and is a novel target for diagnosis and treatment of prostate cancer. (C) 2016 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available