Relationship between LSD1 expression and E-cadherin expression in prostate cancer

被引:24
作者
Wang, Min [1 ]
Liu, Xiuheng [1 ]
Jiang, Guanjun [1 ]
Chen, Hui [1 ]
Guo, Jia [1 ]
Weng, Xiaodong [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Urol, Wuhan 430060, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
LSD1; E-cadherin; Prostate cancer; Progression; Metastases; EPITHELIAL-MESENCHYMAL TRANSITION; ANDROGEN-RECEPTOR; GENE-EXPRESSION; SNAIL; DEMETHYLATION; INVASION;
D O I
10.1007/s11255-015-0915-2
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
To investigate the relationship between the expression of LSD1 and E-cadherin in prostate cancer and their prognostic significance. The expression of LSD1 and E-cadherin in prostate cancer was detected using immunohistochemistry, and the relationship between the expressions of these two molecules was analyzed by correlation analysis. Furthermore, LNCap cell line was treated with Pargyline (an inhibitor of LSD1), and Western blot was used to analyze LSD1 and E-cadherin expression. LSD1 expression increased significantly in prostate cancer specimens compared with benign prostatic hyperplasia (P < 0.05). Further analysis testified that LSD1 expression was positively correlated with higher Gleason Score, distant metastases, and poor prognosis (P < 0.05). Nevertheless, E-cadherin expression decreased significantly in prostate cancer specimens compared with benign prostatic hyperplasia (P < 0.05) and was negatively correlated with higher Gleason Score, distant metastases (P < 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression in prostate cancer (rs = -0.486, P = 0.001). Positive LSD1 expression and negative E-cadherin expression were significantly correlated with high 2-year progression (occurrence of castration-resistant prostate cancer) rate and low 5-year survival rate (P < 0.05). Moreover, Pargyline inhibited activity of LSD1 and up-regulated E-cadherin expression. High LSD1 expression combined with low E-cadherin expression might be predictors of prostate cancer progression and metastasis. Inhibition of LSD1 may be a potential therapeutic target for prevention of prostate cancer.
引用
收藏
页码:485 / 490
页数:6
相关论文
共 34 条
[11]   Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers [J].
Hayami, Shinya ;
Kelly, John D. ;
Cho, Hyun-Soo ;
Yoshimatsu, Masanori ;
Unoki, Motoko ;
Tsunoda, Tatsuhiko ;
Field, Helen I. ;
Neal, David E. ;
Yamaue, Hiroki ;
Ponder, Bruce A. J. ;
Nakamura, Yusuke ;
Hamamoto, Ryuji .
INTERNATIONAL JOURNAL OF CANCER, 2011, 128 (03) :574-586
[12]   Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance [J].
Holzbeierlein, J ;
Lal, P ;
LaTulippe, E ;
Smith, A ;
Satagopan, J ;
Zhang, LY ;
Ryan, C ;
Smith, S ;
Scher, H ;
Scardino, P ;
Reuter, V ;
Gerald, WL .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (01) :217-227
[13]   p53 is regulated by the lysine demethylase LSD1 [J].
Huang, Jing ;
Sengupta, Roopsha ;
Espejo, Alexsandra B. ;
Lee, Min Gyu ;
Dorsey, Jean A. ;
Richter, Mario ;
Opravil, Susanne ;
Shiekhattar, Ramin ;
Bedford, Mark T. ;
Jenuwein, Thomas ;
Berger, Shelley L. .
NATURE, 2007, 449 (7158) :105-U80
[14]   Epithelial-mesenchymal transition in cancer development and its clinical significance [J].
Iwatsuki, Masaaki ;
Mimori, Koshi ;
Yokobori, Takehiko ;
Ishi, Hideshi ;
Beppu, Toru ;
Nakamori, Shoji ;
Baba, Hideo ;
Mori, Masaki .
CANCER SCIENCE, 2010, 101 (02) :293-299
[15]   Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence [J].
Kahl, Philip ;
Gullotti, Lucia ;
Heukamp, Lukas Carl ;
Wolf, Susanne ;
Friedrichs, Nicolaus ;
Vorreuther, Roland ;
Solleder, Gerold ;
Bastian, Patrick J. ;
Ellinger, Joerg ;
Metzger, Eric ;
Schuele, Roland ;
Buettner, Reinhard .
CANCER RESEARCH, 2006, 66 (23) :11341-11347
[16]   Role of Androgen Receptor and Associated Lysine-Demethylase Coregulators, LSD1 and JMJD2A, in Localized and Advanced Human Bladder Cancer [J].
Kauffman, Eric C. ;
Robinson, Brian D. ;
Downes, Martin J. ;
Powell, Leagh G. ;
Lee, Ming Ming ;
Scherr, Douglas S. ;
Gudas, Lorraine J. ;
Mongan, Nigel P. .
MOLECULAR CARCINOGENESIS, 2011, 50 (12) :931-944
[17]   Requirement of the histone demethylase LSD1 in Snail-mediated transcriptional repression during epithelial-mesenchymal transition [J].
Lin, T. ;
Ponn, A. ;
Hu, X. ;
Law, B. K. ;
Lu, J. .
ONCOGENE, 2010, 29 (35) :4896-4904
[18]   The SNAG domain of Snail1 functions as a molecular hook for recruiting lysine-specific demethylase 1 [J].
Lin, Yiwei ;
Wu, Yadi ;
Li, Junlin ;
Dong, Chenfang ;
Ye, Xiaofeng ;
Chi, Young-In ;
Evers, B. Mark ;
Zhou, Binhua P. .
EMBO JOURNAL, 2010, 29 (11) :1803-1816
[19]   The epithelial-mesenchymal transition generates cells with properties of stem cells [J].
Mani, Sendurai A. ;
Guo, Wenjun ;
Liao, Mai-Jing ;
Eaton, Elinor Ng. ;
Ayyanan, Ayyakkannu ;
Zhou, Alicia Y. ;
Brooks, Mary ;
Reinhard, Ferenc ;
Zhang, Cheng Cheng ;
Shipitsin, Michail ;
Campbell, Lauren L. ;
Polyak, Kornelia ;
Brisken, Cathrin ;
Yang, Jing ;
Weinberg, Robert A. .
CELL, 2008, 133 (04) :704-715
[20]   LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription [J].
Metzger, E ;
Wissmann, M ;
Yin, N ;
Müller, JM ;
Schneider, R ;
Peters, AHFM ;
Günther, T ;
Buettner, R ;
Schüle, R .
NATURE, 2005, 437 (7057) :436-439