title: Dishevelled-2 silencing reduces androgen-dependent prostate tumor cell proliferation and migration and expression of Wnt-3a and matrix metalloproteinases.
abstract: To identify Dishevelled-2 (Dvl2) is a prostate cancer-associated gene and analyze the effects on the growth and invasive capacity of human prostate cancer (PCa) cells. Dvl2 mRNA expression was measured in PCa cell lines and tissue samples, by real-time reverse transcription PCR (qRT-PCR). Immunohistochemistry was used to examine the distribution of Dvl2 in PCa specimens. Silencing Dvl2 in LNCaP cells, proliferation was measured by the CCK-8 assay, cell motility and invasiveness by scratch wound and transwell migration assays, and Wnt-3a, AR, and matrix metalloproteinase (MMP) expression by western blotting. Dvl2 was overexpressed in LNCaP cells compared with the AI PCa lines DU-145 and PC-3, as well as in the majority of PCa tissue specimens examined by qRT-PCR (14/27, 51.9 %). Dvl2 expression was low in all 10 BPH specimens, weakly positive in 26/104 AD PCa specimens (23.8 %), positive in 60/104 AD PCa specimens (55 %), and strongly positive in all 5 AI PCa specimens. Dvl2 expression was significantly correlated with combined Gleason score (p = 0.02), lymph node metastasis (p = 0.005), and TNM stage (p = 0.015). Silencing of Dvl2 mRNA expression significantly reduced LNCaP cell proliferation, motility, invasiveness and Wnt-3a, AR, MMP-2, and MMP-9 expression. Dvl2 may increase PCa growth and metastasis potential, possibly by upregulating Wnt-3a, AR, and MMP expression. Silencing Dvl2 expression may be an effective treatment strategy for PCa.
authors: Department of Urology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, People's Republic of China. dryanghui@gmail.com
authors: Yinhui
authors: Y
authors: Yang
authors: Li
authors: L
authors: Jiao
authors: Jianguo
authors: J
authors: Hou
authors: Chuanliang
authors: C
authors: Xu
authors: Linhui
authors: L
authors: Wang
authors: Yongwei
authors: Y
authors: Yu
authors: Yun
authors: Y
authors: Li
authors: Chun
authors: C
authors: Yang
authors: Xia
authors: X
authors: Wang
authors: Yinghao
authors: Y
authors: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D000072261:Dishevelled Proteins; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D060509:Wnt3A Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D060509:Wnt3A Protein; D020782:Matrix Metalloproteinases
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