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ID 110097
Title Alternative
ガレクチン-3は、前立腺癌におけるアンドロゲン受容体シグナル伝達の調節を介して腫瘍進展および抗アンドロゲン剤耐性に関与している
Galectin-3 in Prostate Cancer
Author
Dondoo, Tsogt-ochir Tokushima University
Daizumoto, Kei Tokushima University
Kohzuki, Miho Tokushima University
Kowada, Minoru Tokushima University
Nakatsuji, Hiroyoshi Tokushima University
Keywords
Prostate cancer
galectin-3 gene
anti-androgen resistance
Content Type
Thesis or Dissertation
Description
Background: Castration-resistant prostate cancer (CRPC)-related deaths are increasing worldwide. Therefore, clarification of the mechanisms of hormone-related tumor progression and resistance to anti-androgen drugs is useful in order to develop strategies for appropriate treatment of CRPC. Galectin-3 has been shown to be correlated with tumor progression in a variety of cancer types through the regulation of tumor proliferation, angiogenesis, and apoptosis. Materials and Methods: We examined tumor cell invasion and migration using the xCELLigence system. Control LNCaP and galectin- 3-expressing LNCaP (LNCaP-Gal-3) cells were cultured with androgen-depleted medium with 5% charcoal-stripped serum. Cells were treated for 24 h with or without dihydrotestosterone alone or combined with MDV3100 and bicalutamide; gene profile was then analyzed by microarray analysis and mRNA expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated tumor growth using spheroids and xenograft tumor growth in a mouse model. Results: In vitro, LNCaP-Gal-3 cells promoted both cell migration and invasion in an androgen-independent manner compared to control LNCaP cells. Galectin-3 also enhanced anchorage-independent growth and xenograft tumor growth even after castration. Importantly, galectin-3 greatly enhanced transcriptional activity of the androgen receptor (AR), especially on treatment with dihydrotestosterone. In microarray and qRT-PCR analyses, galectin-3 increased the expression of several AR-target genes, such as kallikreinrelated peptidase 3 (KLK3), and transmembrane protease, serine 2 (TMPRSS2). These AR-target genes were not fully suppressed by anti-androgen drugs such as bicalutamide or MDV3100. Galectin-3 significantly inhibited the effect induced by anti-androgen drugs MDV3100 and bicalutamide, suggesting that galectin-3 may be involved in resistance to anti-androgen drug through enhancement of transcriptional activity of AR and expression of AR-related genes. Conclusion: These results suggest that galectin-3 is a potential target molecule for future treatment of anti-androgen drug-resistant prostate cancer.
Journal Title
ANTICANCER RESEARCH
ISSN
02507005
17917530
NCID
AA10625860
AA12440673
Publisher
The International Institute of Anticancer Research
Volume
37
Issue
1
Start Page
125
End Page
134
Published Date
2017-01
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨:LID201704261001.pdf
論文本文:k3011_fulltext.pdf
本論文は, 著者TSOGT-OCHIR DONDOOの学位論文として提出され, 学位審査・授与の対象となっている。
公開に関する許諾確認は著者・編集事務局間のメールによる。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3011号
Diploma Number
甲医第1315号
Granted Date
2017-02-23
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences